The document discusses the development of lymphocytes, specifically B and T cells, highlighting the importance of antigen receptor gene rearrangement in creating a diverse immune repertoire. It explains the processes of selection in shaping this repertoire, including positive and negative selection, as well as the differentiation of lymphocyte subsets. Additionally, it outlines the organization of immunoglobulin (Ig) and T-cell receptor (TCR) gene loci and the steps involved in V(D)J recombination crucial for lymphocyte maturation.

1. Immunology

2. Lymphocytes Development
• Express a diversity of antigen receptors
• Diversity generated during development of B and
T cells from precursor cells
• Lymphocyte development or lymphocyte
maturation
• Immune repertoire – antigen receptors on B and T
cells
• Central feature of lymphocyte development –
rearangement and expression of antigen receptor
genes

3. Commitment to the B and T cell lineages
• B and T cells (plus others) come from HSCs
• Early B and T cell development is
characterized by the proliferation of
progenitors, stimulated mainly by IL-7
resulting in marked increase in cell numbers

4. Commitment to the B and T cell receptors

5. Antigen receptor gene rearrangement and
expression
• Key event in lymphocyte develepment
• Drives generation of a diverse repertoire
• Upto 107
or more different B and T cell clones,
each with a unique receptor
• The rearrangement events are not dependent on
or influenced by presence of antigens
• Antigen receptors are expressed before
encounter with antigens (clonal selection
hypothesis)

6. Selection processes that shape the B and T
cell repertoire
• Signals delivered through pre-antigen and antigen
receptors for survival and proliferation plus continued
maturation
• Positive selection – receptors with low avidity
• Negative selection – elimination of high avid receptors
in generative organs by apoptosis (clonal deletion)
• Negative selection maintains tolerance (central
tolerance)
• Receptor editing – making further Ig gene
rearrangements to evade self-reactivity

7. Generation of lymphocyte subsets
• Double positive T cells differentiate into either
CD4+ class II MHC or CD8+ MHC I restricted T
cells
• B cells differentiate into either follicular B cells
and mediate T cell-dependent immune
responses in secondary organs or marginal
zone B cells that reside in marginal sinus in the
spleen and mediate largely T cell-independent
responses to blood-borne antigens

8. Rearrangement of antigen receptor genes in
B and T cells
• Genes that encode diverse antigen receptors
of B and T cells are generated by the
rearrangement in individual lymphocytes of
different variable (V) region gene segments
with diversity (D) and/or joining (J) gene
segments (VDJ recombination)

9. Germline organization of Ig and TCR Genes
• Ig and TCR germline organizations are
fundamentally similar
• Characterized by spatial segregation of
sequences that must be joined together to
produce functional genes coding for antigen
receptors

10. Organization of Ig gene loci
• Ig heavy chain, Ig κ chain, and Ig λ chain loci
from different chromosomes code for those
respective proteins
• Organized essentially the same way in all
mammals although may vary on chromosomal
locations, number, and sequence
• Non-coding sequences in the Ig loci play
important roles in recombination and gene
expression.

11. Organization of TCR gene loci
• TCR α chain, TCR β chain, TCR γ chain map to
three seperate loci, and the TCR δ chain locus
is contained within the TCR α locus.

12. V(D)J recombination
• Can be divided into 4 distinct sequential
events
Synapsis
Cleavage
Coding end processing
Joining

13. B lymphocyte development
• Main events are: rearrangement and
expression of Ig genes, selection, and
proliferation

14. Stages of B cell development

15. Maturation of T cells
• Involve sequential rearrangement and
expression of TCR genes, proliferation, antigen
induced selection, and the acquisition of
functional capabilities