The cells of the B line synthesize immunoglobulins. They are either produced at a membrane (on the surface of the B-lymphocytes) or are secreted (by the plasmocytes)
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 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.
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 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.
CLONAL SELECTION THEORY IS AN SCIENTIFIC THEORY IN IMMUNOLOGY THAT EXPALINS THE FUNCTION OF CELLS OF THE IMMUNE SYSTEM IN RESPONSE TO SPECIFIC ANTIGEN INVADING THE BODY.
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.
CLONAL SELECTION THEORY IS AN SCIENTIFIC THEORY IN IMMUNOLOGY THAT EXPALINS THE FUNCTION OF CELLS OF THE IMMUNE SYSTEM IN RESPONSE TO SPECIFIC ANTIGEN INVADING THE BODY.
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.
V(D)J rearrangements and Antigen Antibody interactionsTathagat Sah
This presentation discusses the concept of the generation of antibody diversity through immunoglobulin(Ig) gene rearrangements. The mechanism of V-J rearrangements (light chain) and V-D-J rearrangements (heavy chain) is elaborated in detail along with the Ig constant region rearrangements, called class-switching. The factors dictating antibody diversity and antigen-antibody interactions have also been discussed briefly.
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
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.
Strucure, functions and genetics of immunoglobulinsJESSE OWAKI
The power-point contains summerised concept on Structures, Functions and Genetics of Immunoglobulins.
It is to help my fellow undergraduate students to have a basic understanding on the topic.
Kindly contact me for more materials. Thank you.
Question VI. In 1976, Hozumi and Tonegawa published an elegant paper.pdfbermanbeancolungak45
Question VI. In 1976, Hozumi and Tonegawa published an elegant paper (Proc. Natl. Acad. Sci.
USA 73, 3628-3632, 1976) showing that a V gene and a C gene are miles apart in germline DNA
(from mouse embryos), but next to each other in antibody-coding DNA (from a myeloma tumor).
Subsequent experiments have demonstrated unequivocally that the immune system generates the
antibody diversity by shuffling a few hundred genes to create countless permutations, in a
process called V(D)J recombination. In this process, RAG enzymes work as a multi-subunit
complex to induce cleavage of a double-stranded DNA molecule between the antigen receptor
coding segment and a flanking recombination signal sequence (RSS). They do this in two steps.
They initially introduce a ‘nick’ in the 5\' (upstream) end of the RSS heptamer (a conserved
region of 7 nucleotides) that is adjacent to the coding sequence, leaving behind a 3\'-hydroxyl
group at the coding end and a 5\'-phosphate group at the RSS end. The next step couples these
chemical groups, binding the OH-group (on the coding end) to the PO4group (that is sitting
between the RSS and the gene segment on the opposite strand). [Assess each subsequent
statement (64-71) as either factually correct (= “true”) or incorrect (= “false”)]:
64. This is an important enzymatic step in a process known as somatic recombination, which is
limited to macrophages.
65. This is an event of the mechanism of genetic recombination in the early stages of Ig and
TCRs production.
66. This produces a 3\'-phosphorylated double-stranded break at the RSS and a covalently closed
hairpin at the coding end.
67. This produces a 3\'-phosphorylated double-stranded break at the RSS and a non-covalently
closed hairpin at the coding end.
68. This produces a 5\'-phosphorylated double-stranded break at the RSS and a covalently-closed
hairpin at the coding end.
69. This produces a 5\'-phosphorylated double-stranded break at the RSS and a non-covalently
closed hairpin at the coding end.
70. This is an event of the mechanism of genetic recombination in the late stages of
immunoglobulin (Ig) and T-cell receptors (TCRs) production.
71. The V(D)J recombination events are involved in somatic hypermutations of the TCR and the
binding of the OH-group (on the coding DNA end) to the PO4-group (that is sitting between the
RSS and the gene segment on the opposite DNA strand) plays an important role in these
hypermutations, which contribute to generating TCR diversity.
Solution
64. False
This process is not limited to macrophages and occurs in the B cells and T cells.
65. True
This occurs in early stages of production of T cell receptors as well as immunoglobulins.
66. False
No 3\'-phosphorylated double-stranded break is produced
67. False
No 3\'-phosphorylated double-stranded break is produced
68. True
Yes, 5\'-phosphorylated break is produced at the RSS as well as on the coding end a covalently
closed- hairpin is formed.
69. False
Non- covalently closed hairpin is not .
Structure and function of immunoglobulins(antibodies) Likhith KLIKHITHK1
Immunoglobulins (Ig) or antibodies are glycoproteins that are produced by plasma cells. B cells are instructed by specific immunogens.For, example, bacterial proteins, to differentiate into plasma cells, which are protein-making cells that participate in humoral immune responses against bacteria, viruses, fungi, parasites, cellular antigens, chemicals, and synthetic substances.
The immunogen or antigen reacts with a B-cell receptor (BCR) on the cell surface of B lymphocytes, and a signal is produced that directs the activation of transcription factors to stimulate the synthesis of antibodies, which are highly specific for the immunogen that stimulated the B cell. Furthermore, one clone of B cell makes an immunoglobulin (specificity). Besides, the immune system remembers the antigens that caused a previous reaction (memory) due to the development of memory B cells. These are intermediate, differentiated B cells with the capability to quickly become plasma cells. Circulating antibodies recognize antigen in tissue fluids and serum. This activity describes the physiology and pathophysiology of immunoglobulins
A chart showing the fate of each part of an early embryo, in a particular blastula stage is called fate maps. It is done because the correct interpretation of gastrulation is impossible without the knowledge of the position which are the presumptive germinal layers (Ectoderm, Mesoderm and Endoderm) occupy in blastula.
Fate mapping is a method used in developmental biology to study the embryonic origin of various adult tissues and structures. The "fate" of each cell or group of cells is mapped onto the embryo, showing which parts of the embryo will develop into which tissue. When carried out at single-cell resolution, this process is called cell lineage tracing. It is also used to trace the development of tumors.
DNA sequencing is the process of determining the sequence of nucleotides (A, T, G, and C) in the DNA. It includes method or technology that is used to determine the order of the four bases: adenine, thymine, guanine and cytosine.
The chain-termination method developed by Frederick Sanger and coworkers in 1977. This method used fewer toxic chemicals and lower amounts of radioactivity than the Maxam and Gilbert method. Because of its comparative ease, the Sanger method was soon automated and was the method used in the first generation of DNA sequencers.
published a DNA sequencing method in 1977 based on chemical modification of DNA and subsequent cleavage at specific bases. Also known as chemical sequencing, this method allowed purified samples of double-stranded DNA to be used without further cloning.
Maxam-Gilbert sequencing requires radioactive labeling at one 5' end of the DNA and purification of the DNA fragment to be sequenced. Chemical treatment then generates breaks at a small proportion of one or two of the four nucleotide bases in each of four reactions (G, A+G, C, C+T). The concentration of the modifying chemicals is controlled to introduce on average one modification per DNA molecule. Thus a series of labeled fragments is generated, from the radiolabeled end to the first "cut" site in each molecule. The fragments in the four reactions are electrophoresed side by side in denaturing acrylamide gels for size separation. To visualize the fragments, the gel is exposed to X-ray film for autoradiography, yielding a series of dark bands each corresponding to a radiolabeled DNA fragment, from which the sequence may be inferred.
Cloning is the process of producing genetically identical individuals of an organism either naturally or artificially.
It is the process of taking genetic information from one living thing and creating identical copies of it. The copied material is called a clone.
Nature has been doing it for millions of years. For example, identical twins have almost identical DNA, and asexual reproduction in some plants and organisms can produce genetically identical offspring.
Cloning in biotechnology refers to the process of creating clones of organisms or copies of cells or DNA fragments (molecular cloning).
Bacteriophage- types, structure and morphology of t4 phage, morphogenesisDr. Dinesh C. Sharma
Escherichia virus T4 is a species of bacteriophages that infect Escherichia coli bacteria. It is a member of virus subfamily Tevenvirinae (not to be confused with T-even bacteriophages, which is an alternate name of the species). T4 is capable of undergoing only a lytic lifecycle and not the lysogenic lifecycle.
Each cell of a multicellular organism contain the same genetic material, but the expression of the gene is different in different type of cell group. On the basis of expression requirement they are grouped in to
Structural Gene- Mostly expressed once in a life
Vital Gene- Involved in of vital biochemical processes such as respiration and need to be expressed all the time
Functional Gene- Genes are not expressed all the time. They are switched on an off at need
The regulation of Gene required in case of functional gene and its explained by Francois Jacob, Jacques Monod and Andre Lwoff (Nobal Prize in 1961)
Theory of preformation,
Epigenetic theory,
Theory of pengenesis,
Recapitulation theory,
Germplasm theory,
Mosaic theory,
Regulated theory,
Gradient theory
Theory of organizers.
Sericulture is the cultivation of silkworms to produce silk. Bombyx mori (the caterpillar of the domesticated silk moth) is the most widely used species of silkworms.
A device that computes, especially a programmable electronic machine that performs high-speed mathematical or logical operations or that assembles, stores, correlates, or otherwise processes information.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
NVBDCP.pptx Nation vector borne disease control program
Immunoglobulin Gene Structure
1. Dr. Dinesh C. Sharma,
Associate Professor & Head
Dept of Zoology
Km. Mayawati Govt. Girls P.G. College, Badalpur, Gb nagar
2. An immunoglobulin (Ig) consists
of
2 identical light chains (L)
and
2 identical heavy chains (H)
3. For example IgG-type; at the three-dimensional level, an Ig chain consists of one N-
terminal variable domain, V, and one (for an L chain) or several (for an H chain) C-
terminal constant domain(s), C.
The cells of the B line synthesize immunoglobulins. They are either produced at
a membrane (on the surface of the B-lymphocytes) or are secreted (by the
plasmocytes).
4. 1-Light chains (Kappa)
1.1. Kappa chain: V-J rearrangements
• IGK (kappa) genes at 2p11 on chromosome 2.
• Multiple IGKV genes for the variable region, V (76 genes, of which 31 to 35 are functional); 5 IGKJ genes for the
junctional region, J; 1 IGKC gene for the constant region, C; the V, J and C genes are separated in the DNA of the
genome ('germline' configuration of the Ig genes).
• These are multigene families
• First the DNA is rearranged: this makes it possible to join 1 V and 1 J; the intermediate sequences are then deleted,
• The pre-messenger RNA is copied (transcription); this includes introns,
• Then comes splicing: the elimination of the introns from the pre-messenger RNA , to yield mature, messenger RNA,
• This is followed by protein synthesis (known as 'translation').
Note-
• It is crucial not to confuse DNA rearrangements with RNA splicing.
• Only the genes for the immunoglobulins and T-receptors undergo DNA rearrangement.
IGK
(kappa/Lambda)
V-Region
IGKV
76 Genes
J-Region
IGKJ
5 Genes
C-region
IGKC
1 Gene
5. V-J rearrangements occur at
the recombination signals (RS),
which include a heptameric
sequence (7 nucleotides) and a
nonameric sequence (9
nucleotides), separated by a
spacer.
Each IGKV gene is followed
downstream (in the 3' position)
by an RS consisting of a
CACAGTG heptamer, and then
by a 12-bp spacer, and then an
ACAAAAACC nonamer.
Each IGKJ gene is preceded
upstream (in the 5' position) by
an RS consisting, between 5'
and 3', of a GGTTTTTGT
nonamer, a 23-bp spacer and a
CACTGTG heptamer
Nonameric
sequence
ACAAAAACC
Heptameric
sequence
CACAGTAG
Spacer (12bp)
Nonameric
sequence
GGTTTTTGT
Heptameric
sequence
CACTGTG
Spacer (23bp)
6. 1-Light chains (Lambda)
1.2. Lambda chain: V-J rearrangements
IGL (lambda) genes at the 22q11 position on
chromosome 22;
the V-J rearrangement mechanism is the
same as that described for the IGK genes: the
rearrangements take place between one of the
29 to 33 functional IGLV genes and a J gene;
it should be noted that there are 4 to 5
functional IGLC genes, each of which is
preceded by a IGLJ gene.
1.3. Allele exclusion and isotype
Allele exclusion can be explained in part by
the timing of rearrangements, and partly by
the surface expression of a functional
immunoglobulin, which inhibits the
rearrangements and therefore the expression
of a second chain. Only one 14 chromosome
and one 2 (or 22) chromosome are therefore
productive
7. Recombination signal sequences are conserved sequences of noncoding DNA that
are recognized by the RAG1/RAG2 enzyme complex during V(D)J recombination in
immature B cells and T cells. Recombination signal sequences guide the enzyme
complex to the V, D, and J gene segments that will undergo recombination during the
formation of the heavy and light-chain variable regions in T-cell
receptors and immunoglobulin molecules
RSSs are made up of highly conserved heptamer sequences (7 base
pairs), spacer sequences, and conserved nonamer sequences (9 base pairs) that are
adjacent to the V, D and J sequences in the heavy-chain region of DNA and the V and J
sequences in the light-chain DNA region. Spacer sequences are located between heptamer and
nonamer sequences and exhibit base pair variety but are always either 12 base pairs or 23 base
pairs long. Heptamer sequences are usually CACAGTG and nonamers are
usually ACAAAAACC. The nucleotides in RED are more highly conserved. The RAG1/RAG2
enzyme complex follows the 12-23 rule when joining V, D, and J segments, pairing 12-bp
spacer RSSs to 23-bp spacer RSSs. This prevents two different genes coding for the same
region from recombining (ex. V-V recombination). RSSs are located between V, D, and J
segments of the germ-line DNA of maturing B and T lymphocytes and are permanently spliced
out of the final Ig mRNA product after V(D)J recombination is complete.
8. The RAG1/RAG2 enzyme complex recognizes the heptamer
sequences flanking the V and J coding regions and nicks their 5'
end, releasing the intervening DNA between the V and J coding
regions. In the heavy-chain coding region of DNA, the RAG1/RAG2
enzyme complex recognizes the RSSs flanking the D and J
segments and brings them together, forming a loop containing
intervening DNA. The RAG1/RAG2 complex then introduces a nick
at the 5' end of the RSS heptamers adjacent to the coding regions
on both the D and J segments, permanently removing the loop of
intervening DNA and creating a double-stranded break that is
repaired by VDJ recombinase enzymes. This process is repeated for
the joining of V to DJ. In light-chain rearrangement, only V and J
segments are brought together.
9. • IGH ('heavy') genes at 14q32 on chromosome 14.
• There are 11 IGHC genes, 9 of which are functional (IGHM, IGHD, IGHG1, IGHG2, IGHG3, IGHG4, IGHA1,
IGHA2 and IGHE) and correspond respectively to 9 heavy chain isotypes m, d, g1, g2, g3, g4, a1, a2 and e.
• DNA rearrangements between one of the 38 to 46 functional variable IGHV genes, one of the 23 functional
diversity IGHD genes, and one of the 6 functional junction IGHJ genes: there are also some RSs, which are
located downstream (in position 3') of the V genes, either side of the D genes and upstream (at 5') of the J genes.
During V-D-J rearrangement, a junction is first formed between 1 D and 1 J, and then one between 1 V and the
D-J complex.
2-Heavy chains
Note: there are also 2 or 3 open reading frames
for the D genes; each of which can code for 2 or 3
different peptide sequences. The V-D-J junctions
are also characterized by nucleotide deletions (by
an exonuclease) and by the random addition of
nucleotides (by means of TdT, terminal
deoxynucleotidyl transferase); the V regions
which result are not, therefore, coded in the
genome of the individual and considerably
increase the diversity of the V-D-J junctions of
the variable domains of the heavy chains of the
immunoglobulins.
10. 2.2. Isotype switching
• In the pre-B lymphocyte, a mu chain is first synthesized, because the constant IGHM gene (C) is located near to the V-D-J rearrangement.
This mu chain is associated with the pseudo-light chain and the combination constitutes the pre-B receptor. The first complete Ig
synthesized by the B-lymphocyte is an IgM, in which the mu chain is combined with a light kappa or lambda chain.
• During its differentiation, the B lymphocyte can express some other isotype or sub-isotype of Ig. This involves the replacement of an
IGHC gene by another, as the result of DNA recombination (isotype switch), with the excision of the entire intermediate part of a deletion
loop. This excision occurs at the switch sequences (role related to that of the RSs).
• The usual sequence is then as follows: synthesis of pre-messenger RNA, splicing of the introns, resulting in mature RNA, and then protein
synthesis.
• This explains why 1) a B-lymphocyte can at first synthesize an IgM and then, during its differentiation, an IgG (IgG1, IgG2, IgG3 or
IgG4), an IgA (IgA1 or IgA2) or an IgE, and 2) that it retains the same V-D-J rearrangement and therefore the same antigen recognition
site (idiotype)
11. • Alternative splicing of the pre-messenger RNA of the heavy chain can yield either a
membrane heavy chain (membrane Ig of B lymphocytes), or a secreted heavy chain
(plasmocyte secreted Ig), which retain the same V-D-J rearrangement (idiotype) and the
same constant region (isotype).
• Note: the same mechanism (alternative splicing of a pre-messenger) expresses the IgMs and
IgDs in the same B cell (situation in mature B cells leaving the bone marrow and reach the
lymph nodes via the circulation).
3. Membrane and secreted Igs
12. 1. Germline diversity: multigene families
• 'Germline' diversity depends on the number of genes at each locus. These are families of genes, offering the possibility
of a choice between similar? functional sequences. Possible intergene recombinations permit the long-term evolution of
the locus with duplication or deletion of the genes.
• These genes undergo intragene conversions and recombinations, leading to mixing and diversity (polymorphism)
between individuals.
• The presence of several open reading frames, in the case of IGHD genes, further increases the possibility of choice
between similar functional sequences.
2. Diversity due to DNA rearrangements
• Combination diversity - in the mathematical sense of the term - permits the potential synthesis of a million
immunoglobulins. The IGH genes permit the synthesis of about 6000 heavy chains, the IGK or IGL genes of about 160
light chains, which is equivalent to about a million possible combinations 6 x 10 3 x 160).
In addition to this, during the rearrangements of
the IGH of the heavy chains, the acquisition of
the N regions, and using one or other of the
reading frames for the D genes at the V-D-J
junctions, and during the IGK or IGL
rearrangements of the light chains, flexibility of
the V-J junctions. These mechanisms contribute
to increasing the diversity by a factor 103 to
104 (potential synthesis of 109 Ig chains).
Conclusions
13. 3.Diversity as a result of somatic hypermutations
• Finally, somatic mutations are extremely numerous (somatic hypermutations)
and produce very targeted characterization of the rearranged V-J and V-D-J
genes of the Ig, but their mechanism of onset is not yet known. AID
(activation-induced cytidine deaminase) may be implicated both in the
occurrence of the mutations and the switch mechanism. The mutations
appear during the differentiation of the B lymphocyte in the lymph glands
and contribute to increasing the diversity of the Igs by a further factor of 103,
which makes it possible to achieve a potential diversity of 1012 different Igs.
• These different mechanisms of diversity make it possible to obtain
1012 different immunoglobulins, capable of responding to the several million
known antigens.
• The number of different Igs is in fact limited by the number of B cells in a
given species.