1. Diversity in the germline is expanded by DNA rearrangement in B cells through combinatorial diversity from joining variable, diversity and joining gene segments, as well as junctional diversity from variations in rearrangement.
2. During antigen-independent B cell differentiation, immunoglobulin gene rearrangement begins with D-J joining, followed by V-DJ joining and light chain rearrangement, culminating in expression of IgM on the cell surface.
3. Mature B cells can express both IgM and IgD through alternative RNA splicing of primary gene transcripts for membrane and secreted forms of both antibodies.
The Molecular Genetics Of Immunoglobulinsraj kumar
The document summarizes the molecular genetics of immunoglobulins. It describes how a single constant region gene is encoded separately from multiple variable region genes. A mechanism rearranges the V and C genes so they can fuse to form a complete immunoglobulin gene. This explains how B cells can produce antibodies with different specificities from a finite set of gene segments through combinatorial diversity and junctional diversity during rearrangement. The same specificity can be expressed on the cell surface via a membrane coding sequence or secreted via a secretion coding sequence using alternative polyadenylation sites.
The document summarizes key concepts in antibody synthesis and the physiology of the humoral immune response. It discusses:
1) B cell development from hematopoietic stem cells through transitional and mature naive B cell stages.
2) The mechanisms of immunoglobulin gene rearrangement, including V(D)J recombination and somatic hypermutation.
3) Selection processes in the bone marrow and lymph nodes that establish B cell receptor specificity and diversity.
4) The cellular interactions, molecular signaling, and genetic alterations that drive antibody class switching, somatic hypermutation, and the development of long-lived plasma cells and memory B cells in germinal centers.
The Molecular Genetics Of Immunoglobulinsraj kumar
The document discusses the molecular genetics of immunoglobulins. It describes how a single constant region gene is encoded separately from multiple variable region genes. A mechanism rearranges the V and C genes so they can fuse to form a complete immunoglobulin gene. There are multiple V, D, and J genes that combine in various ways to generate diversity through combinatorial rearrangement. The same antibody specificity can be expressed on the cell surface via one splicing pathway and secreted via another pathway using alternate polyadenylation sites.
This presentation describes the stages of normal development of B and T cells in human. Various cytokines important for these development and different antigen markers expressed in different stages of development are also described. Mechanisms of antibody diversity and mechanisms to prevent autoimmunity are also explained.
The document summarizes key aspects of T cell antigen receptor (TcR) discovery and structure:
1) TcR were discovered through making monoclonal antibodies against the antigen receptor of cloned T cells, which led to identifying the TcR alpha and beta chains.
2) TcR genes rearrange through somatic recombination similar to immunoglobulin genes, generating diversity through combinations of variable, diversity and joining gene segments.
3) Junctional diversity is introduced through addition of non-templated and palindromic nucleotides during the recombination process.
This document discusses the structure, properties, genetic organization, and genetic rearrangement of antibodies which allows for antibody diversity. It notes that antibodies are glycoproteins produced by plasma cells that recognize and bind antigens. Their genetic organization involves genes for heavy and light chains being located on different chromosomes, with multiple gene segments that undergo rearrangement. This rearrangement at the DNA and RNA level involves joining of V, D, and J genes for heavy chains and V and J genes for light chains, and splicing with C region genes to produce different antibody classes. This genetic rearrangement and splicing is essential for producing the antibody diversity needed to recognize a wide range of antigens.
The document discusses immunoglobulin and T cell receptor genetics. It describes:
1) The organization of light and heavy chain gene loci, including multiple V, D, and J genes.
2) The mechanisms of V(D)J recombination and junctional diversity that generate antibody diversity prior to antigen exposure.
3) The processes of heavy and light chain gene rearrangement and expression that produce a single antibody specificity per B cell.
The document summarizes the key mechanisms by which the human immune system generates a diverse repertoire of antibodies from a relatively small number of genes. It describes the somatic variation theory where mutation and recombination of immunoglobulin genes in somatic cells results in high antibody diversity. It explains processes like V(D)J recombination of light and heavy chain genes, junctional diversity, allelic exclusion, somatic hypermutation, and class switching which all contribute to antibody diversity.
The Molecular Genetics Of Immunoglobulinsraj kumar
The document summarizes the molecular genetics of immunoglobulins. It describes how a single constant region gene is encoded separately from multiple variable region genes. A mechanism rearranges the V and C genes so they can fuse to form a complete immunoglobulin gene. This explains how B cells can produce antibodies with different specificities from a finite set of gene segments through combinatorial diversity and junctional diversity during rearrangement. The same specificity can be expressed on the cell surface via a membrane coding sequence or secreted via a secretion coding sequence using alternative polyadenylation sites.
The document summarizes key concepts in antibody synthesis and the physiology of the humoral immune response. It discusses:
1) B cell development from hematopoietic stem cells through transitional and mature naive B cell stages.
2) The mechanisms of immunoglobulin gene rearrangement, including V(D)J recombination and somatic hypermutation.
3) Selection processes in the bone marrow and lymph nodes that establish B cell receptor specificity and diversity.
4) The cellular interactions, molecular signaling, and genetic alterations that drive antibody class switching, somatic hypermutation, and the development of long-lived plasma cells and memory B cells in germinal centers.
The Molecular Genetics Of Immunoglobulinsraj kumar
The document discusses the molecular genetics of immunoglobulins. It describes how a single constant region gene is encoded separately from multiple variable region genes. A mechanism rearranges the V and C genes so they can fuse to form a complete immunoglobulin gene. There are multiple V, D, and J genes that combine in various ways to generate diversity through combinatorial rearrangement. The same antibody specificity can be expressed on the cell surface via one splicing pathway and secreted via another pathway using alternate polyadenylation sites.
This presentation describes the stages of normal development of B and T cells in human. Various cytokines important for these development and different antigen markers expressed in different stages of development are also described. Mechanisms of antibody diversity and mechanisms to prevent autoimmunity are also explained.
The document summarizes key aspects of T cell antigen receptor (TcR) discovery and structure:
1) TcR were discovered through making monoclonal antibodies against the antigen receptor of cloned T cells, which led to identifying the TcR alpha and beta chains.
2) TcR genes rearrange through somatic recombination similar to immunoglobulin genes, generating diversity through combinations of variable, diversity and joining gene segments.
3) Junctional diversity is introduced through addition of non-templated and palindromic nucleotides during the recombination process.
This document discusses the structure, properties, genetic organization, and genetic rearrangement of antibodies which allows for antibody diversity. It notes that antibodies are glycoproteins produced by plasma cells that recognize and bind antigens. Their genetic organization involves genes for heavy and light chains being located on different chromosomes, with multiple gene segments that undergo rearrangement. This rearrangement at the DNA and RNA level involves joining of V, D, and J genes for heavy chains and V and J genes for light chains, and splicing with C region genes to produce different antibody classes. This genetic rearrangement and splicing is essential for producing the antibody diversity needed to recognize a wide range of antigens.
The document discusses immunoglobulin and T cell receptor genetics. It describes:
1) The organization of light and heavy chain gene loci, including multiple V, D, and J genes.
2) The mechanisms of V(D)J recombination and junctional diversity that generate antibody diversity prior to antigen exposure.
3) The processes of heavy and light chain gene rearrangement and expression that produce a single antibody specificity per B cell.
The document summarizes the key mechanisms by which the human immune system generates a diverse repertoire of antibodies from a relatively small number of genes. It describes the somatic variation theory where mutation and recombination of immunoglobulin genes in somatic cells results in high antibody diversity. It explains processes like V(D)J recombination of light and heavy chain genes, junctional diversity, allelic exclusion, somatic hypermutation, and class switching which all contribute to antibody diversity.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
The document discusses the generation of antibody diversity in the immune system. It explains that there are millions of possible antigens but only a small number of immunoglobulin genes in our genome. Through seven mechanisms, including multiple germline genes, combinatorial V(D)J joining, junctional flexibility, and somatic hypermutation, the immune system is able to generate a diverse repertoire of antibodies against all potential antigens from a limited set of gene segments. These mechanisms operate during B cell development and maturation in the bone marrow and lymphoid tissues.
The development of B cells progresses through six stages defined by the rearrangement and expression of immunoglobulin genes in the bone marrow and secondary lymphoid tissues. In the bone marrow, B cells undergo successive gene rearrangements of the heavy and light chain loci, with productive rearrangements allowing the cells to progress while unproductive rearrangements may lead to additional rearrangements or cell death if none are productive. Expression of rearranged immunoglobulin genes terminates further rearrangement and allows the cells to mature and migrate to secondary lymphoid tissues to complete development.
The document summarizes key aspects of T cell antigen receptor (TcR) structure and generation of diversity. It describes how TcR were discovered using monoclonal antibodies that recognize unique structures on T cell clones. TcR are heterodimers composed of α and β chains that are similar to antibody structures but do not undergo somatic hypermutation. TcR diversity is generated through combinatorial rearrangement of variable (V), diversity (D), and joining (J) gene segments, as well as junctional diversity from imprecise joining and addition of untemplated nucleotides.
Somatic hypermutation and affinity maturationMiriya Johnson
This document discusses affinity maturation, which is the process by which B-cells produce antibodies with increased affinity for antigens during an immune response. It occurs through two main processes: somatic hypermutation and clonal selection. Somatic hypermutation introduces mutations in antibody genes, and clonal selection competitively favors B-cells that produce antibodies with higher antigen affinity. Affinity maturation enhances the antibody response and is critical for vaccine-induced immunity.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
Antibody structure and the generation of b cellCae Upr Cayey
Antibodies are proteins produced by B cells that recognize and bind to pathogens. The document discusses antibody structure, including the variable and constant regions that allow for a diverse range of antigen binding. B cell diversity is generated through random recombination of gene segments and somatic mutations after exposure to antigen. The various antibody isotypes have different functions, with IgM being the initial response and IgG providing longer-term protection. Antibodies can combat infection through neutralization, opsonization, and activation of the complement system.
Antibody diversity presentation is created by creative biolabs. In the slideshare, we will detailed the mechanism of antibody divesity-gene rearrangement and antibody sequencing service. Principle of antibody diversity is completely understood. There is very close relationship in amino acide sequence and antibody function. As we know, there is huge diverse function between two antibodies which have almost same amino acid even if one amino acide is different. If you have any quesion, welcome to cantact us at info@creative-biolabs.com.
- B cell development begins with stem cells in the bone marrow, where they undergo a series of differentiation stages defined by immunoglobulin gene rearrangement under the influence of cytokines and contact with stromal cells.
- Successful rearrangement of the heavy and light chain genes leads to expression of a B cell receptor (BCR) and selection of clones that do not recognize self-antigens through deletion, anergy or receptor editing.
- Mature B cells that pass self-tolerance checkpoints are exported from the bone marrow to the peripheral immune system.
The document discusses B cell development in the bone marrow. Key points:
- B cell development starts in the fetal liver and continues in the bone marrow post-birth, where it undergoes various stages defined by immunoglobulin gene rearrangements.
- Ligation of the pre-B cell receptor by an unknown ligand is essential, as it ensures each cell expresses only one antibody specificity via allelic exclusion and drives proliferation of pre-B cells.
- Mature B cells exit the bone marrow with the ability to bind antigen, and mechanisms exist to ensure tolerance by deleting or anergizing self-reactive B cells.
Mechanism of vd(j) recombination and generation of antibody diversityKayeen Vadakkan
The document summarizes the mechanism of V(D)J recombination and generation of antibody diversity. It discusses:
1) How V(D)J recombination involves rearrangement of one V, D (only in heavy chains), and J gene segment in B and T lymphocytes, bringing them under the control of regulatory elements.
2) The recognition signals and rearrangement process, which involves double stranded breaks and joining of coding ends.
3) The four main stages of V(D)J recombination - synapsis, cleavage, hairpin opening and end processing, and joining.
4) The seven means by which antibody diversity is generated - multiple gene segments, combinatorial joining, junctional flexibility
The ppt covers the following topic-
1.Introduction about antibody.
2. Types of antibody.
3.Genetic basis of antibody diversity.
4. Antibody diversity.
5.Light chain gene segment.
6. Mechanism of variable region DNA rearrangment.
7. Heavy chain gene segment.
8.Alternate splicing.
1. Hematopoietic stem cells give rise to common lymphoid progenitors which differentiate into pro-B and pro-T cells.
2. Commitment to the B or T cell lineage is regulated by distinct transcription factors and cytokines direct proliferation of early lymphocytes.
3. Positive and negative selection during maturation ensure lymphocytes express functional receptors with low self-reactivity.
This document discusses B lymphocytes and their generation, differentiation, and maturation. It contains the following key points:
- B lymphocytes comprise 30% of circulating lymphocytes and about 1 billion are produced daily in the bone marrow.
- B cell development starts from hematopoietic stem cells and involves gene rearrangements leading through various stages from pro-B cells to immature B cells.
- Maturation can occur independently in the bone marrow or depend on antigen exposure in the periphery, leading to plasma cells and memory B cells. Class switching allows expression of different antibody classes.
- Activation can occur through T cell dependent or independent pathways, influencing the strength and type of antibody response.
Antibody class switching is a biological mechanism that changes a B cell's production of antibodies from one class to another, such as from IgM to IgG. It involves changing the constant region of the antibody heavy chain through DNA recombination, while retaining the same variable region and antigen specificity. Double-stranded breaks are generated in switch regions of DNA upstream of constant region genes. DNA is cleaved at two switch regions and the intervening DNA is deleted, allowing substitution of a different constant region exon and changing the class of antibody produced. The free DNA ends are joined by non-homologous end joining to link the variable region to the new constant region gene. This allows a B cell to produce different antibody classes while recognizing
B cell generation-activation_and_differentiationDUSHYANT KUMAR
B cells develop through several stages:
1) Generation in the bone marrow or fetal liver
2) Activation in the lymph nodes through interaction with antigens and T cells
3) Differentiation into plasma cells, which secrete antibodies, or memory B cells
The key events in B cell activation and differentiation are Ig gene rearrangement, affinity maturation through somatic hypermutation, class switch recombination, and formation of plasma cells and memory cells mediated by AID and specific cytokines in germinal centers. B cells can be activated through T cell dependent or independent pathways.
This document summarizes the role of NF-kB proteins in B lymphocytes. It begins with an overview of B cell biology, describing their development from stem cells in the bone marrow or fetal liver. Immature B cells undergo processes like receptor editing to eliminate self-reactivity before migrating to peripheral tissues as mature B cells. The document then examines the specific roles of NF-kB in three areas: B cell development, mature B cell survival, and B cell function. It concludes by noting the need to further understand NF-kB mediated gene expression in B cells.
1) Susumu Tonegawa devised an experiment to test whether immunoglobulin genes undergo rearrangement during B cell development.
2) He isolated DNA from mouse embryonic cells and B cells and separated the DNA fragments by size using gel electrophoresis.
3) He used RNA probes specific for either the entire immunoglobulin gene or just the constant region to detect which DNA fragments contained each region.
4) He found that the two regions were on separate fragments in embryonic DNA but together on one fragment in B cell DNA, demonstrating that rearrangement joins the two regions during B cell development.
This document discusses the genetics of antibody diversity. It describes three main mechanisms that generate antibody diversity: somatic recombination, somatic hypermutation, and class switching. Somatic recombination involves randomly combining variable, diversity, and joining gene segments to generate a wide variety of antibody sequences. Somatic hypermutation further introduces random mutations during B cell activation, allowing higher affinity antibodies to be selected. Class switching changes the constant region of the antibody to alter effector functions. These three processes together allow the immune system to generate a vast repertoire of antibodies with unique specificities.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
The document discusses the generation of antibody diversity in the immune system. It explains that there are millions of possible antigens but only a small number of immunoglobulin genes in our genome. Through seven mechanisms, including multiple germline genes, combinatorial V(D)J joining, junctional flexibility, and somatic hypermutation, the immune system is able to generate a diverse repertoire of antibodies against all potential antigens from a limited set of gene segments. These mechanisms operate during B cell development and maturation in the bone marrow and lymphoid tissues.
The development of B cells progresses through six stages defined by the rearrangement and expression of immunoglobulin genes in the bone marrow and secondary lymphoid tissues. In the bone marrow, B cells undergo successive gene rearrangements of the heavy and light chain loci, with productive rearrangements allowing the cells to progress while unproductive rearrangements may lead to additional rearrangements or cell death if none are productive. Expression of rearranged immunoglobulin genes terminates further rearrangement and allows the cells to mature and migrate to secondary lymphoid tissues to complete development.
The document summarizes key aspects of T cell antigen receptor (TcR) structure and generation of diversity. It describes how TcR were discovered using monoclonal antibodies that recognize unique structures on T cell clones. TcR are heterodimers composed of α and β chains that are similar to antibody structures but do not undergo somatic hypermutation. TcR diversity is generated through combinatorial rearrangement of variable (V), diversity (D), and joining (J) gene segments, as well as junctional diversity from imprecise joining and addition of untemplated nucleotides.
Somatic hypermutation and affinity maturationMiriya Johnson
This document discusses affinity maturation, which is the process by which B-cells produce antibodies with increased affinity for antigens during an immune response. It occurs through two main processes: somatic hypermutation and clonal selection. Somatic hypermutation introduces mutations in antibody genes, and clonal selection competitively favors B-cells that produce antibodies with higher antigen affinity. Affinity maturation enhances the antibody response and is critical for vaccine-induced immunity.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
Antibody structure and the generation of b cellCae Upr Cayey
Antibodies are proteins produced by B cells that recognize and bind to pathogens. The document discusses antibody structure, including the variable and constant regions that allow for a diverse range of antigen binding. B cell diversity is generated through random recombination of gene segments and somatic mutations after exposure to antigen. The various antibody isotypes have different functions, with IgM being the initial response and IgG providing longer-term protection. Antibodies can combat infection through neutralization, opsonization, and activation of the complement system.
Antibody diversity presentation is created by creative biolabs. In the slideshare, we will detailed the mechanism of antibody divesity-gene rearrangement and antibody sequencing service. Principle of antibody diversity is completely understood. There is very close relationship in amino acide sequence and antibody function. As we know, there is huge diverse function between two antibodies which have almost same amino acid even if one amino acide is different. If you have any quesion, welcome to cantact us at info@creative-biolabs.com.
- B cell development begins with stem cells in the bone marrow, where they undergo a series of differentiation stages defined by immunoglobulin gene rearrangement under the influence of cytokines and contact with stromal cells.
- Successful rearrangement of the heavy and light chain genes leads to expression of a B cell receptor (BCR) and selection of clones that do not recognize self-antigens through deletion, anergy or receptor editing.
- Mature B cells that pass self-tolerance checkpoints are exported from the bone marrow to the peripheral immune system.
The document discusses B cell development in the bone marrow. Key points:
- B cell development starts in the fetal liver and continues in the bone marrow post-birth, where it undergoes various stages defined by immunoglobulin gene rearrangements.
- Ligation of the pre-B cell receptor by an unknown ligand is essential, as it ensures each cell expresses only one antibody specificity via allelic exclusion and drives proliferation of pre-B cells.
- Mature B cells exit the bone marrow with the ability to bind antigen, and mechanisms exist to ensure tolerance by deleting or anergizing self-reactive B cells.
Mechanism of vd(j) recombination and generation of antibody diversityKayeen Vadakkan
The document summarizes the mechanism of V(D)J recombination and generation of antibody diversity. It discusses:
1) How V(D)J recombination involves rearrangement of one V, D (only in heavy chains), and J gene segment in B and T lymphocytes, bringing them under the control of regulatory elements.
2) The recognition signals and rearrangement process, which involves double stranded breaks and joining of coding ends.
3) The four main stages of V(D)J recombination - synapsis, cleavage, hairpin opening and end processing, and joining.
4) The seven means by which antibody diversity is generated - multiple gene segments, combinatorial joining, junctional flexibility
The ppt covers the following topic-
1.Introduction about antibody.
2. Types of antibody.
3.Genetic basis of antibody diversity.
4. Antibody diversity.
5.Light chain gene segment.
6. Mechanism of variable region DNA rearrangment.
7. Heavy chain gene segment.
8.Alternate splicing.
1. Hematopoietic stem cells give rise to common lymphoid progenitors which differentiate into pro-B and pro-T cells.
2. Commitment to the B or T cell lineage is regulated by distinct transcription factors and cytokines direct proliferation of early lymphocytes.
3. Positive and negative selection during maturation ensure lymphocytes express functional receptors with low self-reactivity.
This document discusses B lymphocytes and their generation, differentiation, and maturation. It contains the following key points:
- B lymphocytes comprise 30% of circulating lymphocytes and about 1 billion are produced daily in the bone marrow.
- B cell development starts from hematopoietic stem cells and involves gene rearrangements leading through various stages from pro-B cells to immature B cells.
- Maturation can occur independently in the bone marrow or depend on antigen exposure in the periphery, leading to plasma cells and memory B cells. Class switching allows expression of different antibody classes.
- Activation can occur through T cell dependent or independent pathways, influencing the strength and type of antibody response.
Antibody class switching is a biological mechanism that changes a B cell's production of antibodies from one class to another, such as from IgM to IgG. It involves changing the constant region of the antibody heavy chain through DNA recombination, while retaining the same variable region and antigen specificity. Double-stranded breaks are generated in switch regions of DNA upstream of constant region genes. DNA is cleaved at two switch regions and the intervening DNA is deleted, allowing substitution of a different constant region exon and changing the class of antibody produced. The free DNA ends are joined by non-homologous end joining to link the variable region to the new constant region gene. This allows a B cell to produce different antibody classes while recognizing
B cell generation-activation_and_differentiationDUSHYANT KUMAR
B cells develop through several stages:
1) Generation in the bone marrow or fetal liver
2) Activation in the lymph nodes through interaction with antigens and T cells
3) Differentiation into plasma cells, which secrete antibodies, or memory B cells
The key events in B cell activation and differentiation are Ig gene rearrangement, affinity maturation through somatic hypermutation, class switch recombination, and formation of plasma cells and memory cells mediated by AID and specific cytokines in germinal centers. B cells can be activated through T cell dependent or independent pathways.
This document summarizes the role of NF-kB proteins in B lymphocytes. It begins with an overview of B cell biology, describing their development from stem cells in the bone marrow or fetal liver. Immature B cells undergo processes like receptor editing to eliminate self-reactivity before migrating to peripheral tissues as mature B cells. The document then examines the specific roles of NF-kB in three areas: B cell development, mature B cell survival, and B cell function. It concludes by noting the need to further understand NF-kB mediated gene expression in B cells.
1) Susumu Tonegawa devised an experiment to test whether immunoglobulin genes undergo rearrangement during B cell development.
2) He isolated DNA from mouse embryonic cells and B cells and separated the DNA fragments by size using gel electrophoresis.
3) He used RNA probes specific for either the entire immunoglobulin gene or just the constant region to detect which DNA fragments contained each region.
4) He found that the two regions were on separate fragments in embryonic DNA but together on one fragment in B cell DNA, demonstrating that rearrangement joins the two regions during B cell development.
This document discusses the genetics of antibody diversity. It describes three main mechanisms that generate antibody diversity: somatic recombination, somatic hypermutation, and class switching. Somatic recombination involves randomly combining variable, diversity, and joining gene segments to generate a wide variety of antibody sequences. Somatic hypermutation further introduces random mutations during B cell activation, allowing higher affinity antibodies to be selected. Class switching changes the constant region of the antibody to alter effector functions. These three processes together allow the immune system to generate a vast repertoire of antibodies with unique specificities.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
From studies and predictions such as Dreyer and Bennett's, it shows that the light chains and heavy chains are encoded by separate multigene families on different chromosomes. They are referred to as gene segments and are separated by non-coding regions. The rearrangement and organization of these gene segments during the maturation of B cells produce functional proteins. The entire process of rearrangement and organization of these gene segments is the vital source where our body immune system gets its capabilities to recognize and respond to variety of antigens.
Antibody diversity with special emphasis on v(d)j recombinationsourinadhikary
The document discusses antibody diversity and the mechanism of V(D)J recombination. It explains that there are millions of antigens but the immune system can produce specific antibodies against all of them through V(D)J recombination. This process involves random rearrangement of V, D, and J gene segments which combines with junctional diversity to generate the vast number of antibody variants needed. The key steps of V(D)J recombination are described in detail, including recognition of recombination signal sequences, single-strand DNA cleavage, hairpin formation, opening of hairpins, and ligation.
B cell development involves rearrangement of immunoglobulin genes to generate a diverse repertoire of B cell receptors. B cells undergo various stages of development in the bone marrow, with progression dependent on successful rearrangement of heavy and light chain genes and expression of specific cell surface markers at each stage. Mature B cells expressing functional B cell receptors then undergo selection processes upon antigen exposure, leading to differentiation into antibody-secreting plasma cells or memory B cells through clonal selection and proliferation.
This presentation aims to describe the variability present in antibodies.what the Ig superfamily have in common and the various functions it performs.Role of different enzymes imparting diversity to the variable region has been covered.
This document discusses B cell development and antibody-dependent immune responses. It describes how B cells develop in the bone marrow through somatic recombination and rearrangement of immunoglobulin genes. The stages of B cell development are outlined, from stem cells to mature B cells. Clonal selection theory is also summarized, where antigen exposure selects for B cell clones to proliferate and differentiate into antibody-secreting plasma cells or memory B cells. The document further discusses B cell activation mechanisms, immunoglobulin diversity, and the kinetics of primary and secondary immune responses.
The immune system protects the body from infection through two types of immunity: humoral immunity which involves antibodies, and cellular immunity mediated by T cells. Antibodies are Y-shaped proteins produced by B cells that bind to pathogens and mark them for destruction. T cells respond to antigens on the surfaces of cells and regulate the immune response. The immune system has the ability to recognize self from non-self through genetic mechanisms that allow for tremendous diversity in antibody and T cell receptor production through somatic recombination and mutation.
Diversity in receptor and Immunoglobulin [Autosaved].pptxaksilentkiller51
The document summarizes the generation of diversity in B and T cell receptors through various mechanisms during lymphocyte development and maturation. It discusses:
1) Variable (V), diversity (D), and joining (J) gene segments that undergo rearrangement and recombination to generate a diverse repertoire of antigen receptors.
2) Combinatorial diversity through random combinations of rearranged gene segments.
3) Junctional diversity introduced by addition or deletion of nucleotides at junctions.
4) Somatic hypermutation that further diversifies variable regions within germinal centers.
- Antibodies are Y-shaped proteins produced by B cells that recognize and bind to pathogens. They have great diversity and specificity that allows them to target a wide range of antigens.
- Antibodies are composed of two heavy chains and two light chains that form an antigen binding site. The variable regions of the heavy and light chains are responsible for binding to different antigens.
- Monoclonal antibodies are produced from a single clone of B cells and have identical antigen specificity, allowing them to be used as standardized reagents for research and medical purposes. They are produced by fusing B cells with myeloma cells to form immortal hybridomas.
One of the important parts in the study of Immunology.I prepared it for the sake of a seminar series competition conducted in my university. Now I thought of sharing it with others.
The document discusses the genetic basis of antibody diversity. It begins by defining key terms and describing the structure of antibody molecules. There are three families of immunoglobulin genes that encode the heavy chains, kappa chains, and lambda chains. Each gene cluster contains variable and constant region genes. During B cell development, V, D, and J gene segments undergo rearrangement to generate diversity. Additional diversity is created through junctional flexibility, addition of random nucleotides, and somatic hypermutation. This allows over a million combinations of heavy and light chains and an antibody repertoire of over 1 billion different antibodies. Isotype switching allows the same antigen specificity but a different class or isotype of antibody to be produced. Understanding immunoglobulin structure has enabled advances
Group 2 students - Wajjiha Amjad, Ayesha Ishtiaq, Sheeza Arif, and Shabana Noor - submitted a report on antibodies to Dr. Sadaf. The report defines antibodies and discusses their structure, including heavy and light chains that form a Y-shape. It also describes how antibodies bind to antigens and the variable and constant regions that determine specificity and effector functions. Furthermore, it explains how somatic hypermutation and VDJ recombination increase antibody diversity to target the wide range of pathogens encountered. The report concludes that monoclonal antibodies are better for therapeutic applications while polyclonal antibodies are generally preferable for research due to advantages in tolerance and epitope recognition.
This document summarizes key aspects of antibody-dependent responses and B cell development. It discusses how B cells rearrange immunoglobulin genes to generate a diverse repertoire of antibody specificities. The stages of B cell development are outlined, from early pro-B cells to mature B cells. The mechanisms that generate antibody diversity, such as VDJ recombination, junctional diversity, allelic exclusion and isotype switching are described. The kinetics of primary and secondary immune responses are compared. The roles of T cell help and CD40-CD40L interactions in B cell activation are also summarized.
The document discusses the mechanisms by which the immune system generates antibody diversity to recognize millions of antigens. It describes 7 mechanisms: 1) use of multiple gene segments for light and heavy chains, 2) combinatorial V-J and V-D-J joining of gene segments, 3) addition of P-nucleotides and N-nucleotides during joining to introduce junctional diversity, 4) junctional flexibility in joining segments, 5) combinatorial association of paired heavy and light chains, 6) somatic hypermutation of variable regions within germinal centers, and 7) clonal selection of B cells with higher affinity antibodies. Together, these mechanisms allow the immune system to produce a vast repertoire of antibodies despite having relatively few antibody gene segments
T cells recognize antigens through their T cell receptor, which is composed of two different chains and has one antigen-binding site. During T cell development in the thymus, gene rearrangement produces variability in the variable regions of the T cell receptor to recognize a wide range of antigens. When a T cell is stimulated by its antigen, there is no further mutation or switching of immunoglobulin constant region isotypes. T cell receptors function solely as antigen recognition molecules on the cell surface.
Generation of Antibody Diversity- Quick revision from Kuby through presentationSharmistaChaitali
Immunology, Kuby's fifth edition notes for strong background in the topic, General introduction, Types of Antibody and Structure, Experiments, Mechanisms
Antibody, Y shaped protein complex belonging to immunoglobulin (Ig) superfamily, exists in many kinds of organisms, especially higher animals. Specific antibody can bind specifically to particular exogenous pathogen like virus or bacteria to either directly neutralize the pathogens by blocking its active sites or facilitate the elimination of pathogens by other immune cells, such as macrophages. Antibody is produced by B lymphocytes (plasma cells). B cells initially express antibodies on the cell membrane as B cell receptors (BCR). When BCRs are coupled with desired pathogens, B cells are differentiated into plasma cells, producing a myriad of antibodies. Part of plasma cells transform into memory cells which respond relatively fast to the same substance upon later infection. https://www.creative-biolabs.com/antibody-antigen-faq.htm
Similar to 02.11.09(a): Joining Variable & Constant Region Genes (20)
This is a lecture by Joe Lex, MD from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc. Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/.
This is a lecture by Jim Holliman, MD from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc. Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/.
This is a lecture by Joe Lex, MD from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc. Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/.
GEMC- Alterations in Body Temperature: The Adult Patient with a Fever- Reside...Open.Michigan
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02.11.09(a): Joining Variable & Constant Region Genes
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4. 1. How is diversity in the germline further
expanded by DNA rearrangement in B cells?
2. What are the changes in immunoglobulin
gene rearrangement associated with various
stages of antigen-independent B cell
differentiation?
3. How can IgM and IgD be expressed
simultaneously on the surface of a mature,
but naive, B cell?
5. Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Note multiple Cλ genes, each with one J region.
Heavy chain: D segments encode 2-8 amino
acids and are both preceded and followed by
recombination signal sequences. The heavy
chain variable region encodes amino acids 1-99
and JH encodes an additional 14-20 amino acids.
6. Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
7. Methods to generate diversity.
1. Germline diversity is generated by the use of any
one of the one hundred variable region genes,
several Ds, and four to ten Js encoded in DNA.
2. Combinatorial diversity is generated by joining of
any variable region gene to any D to any J, and by
combination of any heavy chain variable region with
any light chain variable region.
50 V x 30 D x 6 JH = 9000 different VH
40 V x 5 Jκ = 200 different Vκ
9000 x 200 = 2x106 binding sites
9000 x 300 = 3x106 binding site (VHVλ)
8. 3. Junctional diversity is generated during V(D)J joining by
variation in the exact point of recombination between a heavy
chain variable region gene and a D segment, or a D segment
and a heavy chain J segment, or a light chain variable region
gene and J segment.
9. Germline sequences:
CCC GGA CGA AGC TTC GTG A CACAGTG VH
DJ CACTGTG GAT TAC TAC GGT AGT : TGG GAC
Cutting next to CACAGTG Cut
CCC GGA CGA AGC TTC GTG A CACAGTG
CACTGTG GAT TAC TAC GGT AGT : TGG
Cut
Ligation of CACAGTG to CACAGTG
CACTGTG:CACAGTG
10. Exonuclease digestion of coding sequences from ends
CCC GGA CGA AGC TTC GTG A GAT TAC TAC GGT AGT
CCC GGA CGA AGC T AT TAC TAC GGT AGT
Ligation of coding ends
CCC GGA CGA AGC T : AT TAC TAC GGT AGT
11. Digestion to a different extent and ligation
CCC GGA CGA AGC TTC GTG A GAT TAC TAC GGT AGT
CCC GGA CGA AGC TTC GT T TAC TAC GGT AGT
CCC GGA CGA AGC TTC GT : T TAC TAC GGT AGT
CCC GGA CGA AGC T : AT TAC TAC GGT AGT
(for comparison; this is the sequence from the previous slide)
Junctional diversity often results in exactly the same
number of codons at the V(D)J junction (particularly in
the light chain variable region), but a different
sequence, and hence, a different amino acid.
12. 4. N region addition occurs by addition of
nucleotides by terminal deoxynucleotide
transferase to variable region, D segment, or J
segment ends. These nucleotides are not
encoded by a template.
CCC GGA CGA AGC TTC GTG A GAT TAC TAC GGT AGT
CCC GGA CGA AGC TT T TAC TAC GGT AGT
CCC GGA CGA AGC TT : GCC T TAC TAC GGT AGT
CCC GGA CGA AGC TT : GCC : T TAC TAC GGT AGT
13. When in B cell differentiation do immunoglobulin
gene rearrangements take place?
Immature Mature
Stem cell Pro B cell Pre B cell B cell B cell
Y Y Y
µ
IgD and IgM
µ chain in IgM on on cell
Absent Absent cytoplasm cell surface surface
University of Michigan Department of Microbiology and Immunology
14. In pro B cells in the bone marrow, during antigen-
independent B cell differentiation, first a D segment
is rearranged to a heavy chain J segment on both
chromosomes.
Then, a heavy chain variable region is rearranged to
the DJ on one chromosome.
If this V(D)J rearrangement does not result in
mu heavy chain expression (because a heavy chain
variable region pseudogene is used, or the VDJ
exon is out of frame), the pro B cell attempts to
rearrange a heavy chain variable region to DJ on
the other chromosome.
15. Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
16. If heavy chain variable region to DJ joining
results in expression of a µ heavy chain,
the pro B cell becomes a pre B cell and also
attempts light chain variable region to J
segment rearrangement on one
chromosome
17. Immature Mature
Stem cell Pro B cell Pre B cell B cell B cell
Y Y Y
µ
IgD and IgM
µ chain in IgM on on cell
Absent Absent cytoplasm cell surface surface
University of Michigan Department of Microbiology and Immunology
18. Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
In general Vκ to Jκ precedes Vλ to Jλ,
because κ rearrangement is favored
20 to 1 over λ rearrangement.
19. Each cell has four light chain loci that could
undergo variable region to J segment
rearrangement. There are several VJ
rearrangements possible in each light chain
locus.
---Vκ20---Vκ21---Vκ22---Vκ23Jκ2---Jκ3---Jκ4---Jκ5---Cκ----
---Vκ20---Vκ21Jκ4---Jκ5---Cκ----
20. If light chain variable region to J segment
joining results in light chain production
and an assembled IgM molecule on the cell
surface, the pre B cell goes on to be an
immature B cell.
21. Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
22. If V(D)J joining results in expression of a mu
heavy chain (the joining is in-frame, and does
not use a pseudo VH), then further VH to DJ
joining is shut off.
If VL to JL joining results in expression of a light
chain, then further VL to JL joining is shut off for
both the kappa and lambda genes.
This feed-back regulation of V(D)J joining is the
basis of allelic exclusion. The shut-off of further
V(D)J joining prevents a B cell from expressing
two heavy chains or two light chains.
23. How does a mature B cell express first the
membrane form of IgM, and later, the secreted
form of IgM, with the same idiotype (same
heavy chain variable region)?
Secreted mu: P V 1 2 3 4 20 aa
Membrane mu: P V 1 2 3 4 41 aa
6/12-;26 uncharged;2/3+
P = the hydrophobic, 26 amino acid, region that is cleaved off
as the translated protein crosses the endoplasmic reticulum.
24. SC=20 aa
MC=41 aa
Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
25. Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
26. Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
27. Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Changes in membrane µ, secreted µ, and
membrane δ expression are mediated by RNA
splicing; the genes themselves do not change.
Hence, these changes in expression are
reversible.
28. Summary
1. Combinatorial diversity is generated by joining of one of
many variable regions to one of a few D segments and J
segments, independently of antigenic stimulation.
2. Junctional and N region diversity are generated at V-D,
D-J, and VL-JL junctions.
3. V(D)J joining is regulated in that it occurs only in the B
cell lineage, the gene segments are recombined in
specific order, and V(D)J joining is stopped by productive
expression of heavy and light chain protein.
4. Membrane µ, secreted µ, and δ expression are mediated
by RNA splicing.
29. Additional Source Information
for more information see: http://open.umich.edu/wiki/CitationPolicy
Slide 6: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Slide 7: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Slide 13: University of Michigan Department of Microbiology and Immunology
Slide 15: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Slide 17: University of Michigan Department of Microbiology and Immunology
Slide 18: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Slide 21: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Slide 24: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Slide 25: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Slide 26: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997
Slide 27: Janeway. Immunobiology: The Immune System in Health and Disease. Current Biology Ltd./Garland Publishing, Inc. 1997