Lymphocyte Development and Antigen Receptor Gene Rearrangement Chapter 8.

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Lymphocyte Development and Antigen Receptor Gene Rearrangement Chapter 8

Stages of lymphocyte maturation

Pluripotent stem cells give rise to distinct B and T lineages

Epigenetics, MicroRNAs, and Lymphocyte Development Many nuclear events in lymphocyte development are regulated by epigenetic mechanisms Epigenetics refers to mechanisms that control gene expression (as well as gene rearrangement in developing lymphocytes) that go beyond the actual sequence of DNA in individual genes The mechanisms that make genes available or unavailable in chromatin are considered to be epigenetic mechanisms including DNA methylation on certain cytosine residues that generally silences genes, post-translational modifications of the histone tails of nucleosomes (e.g., acetylation, methylation, and ubiquitination

Checkpoints in lymphocyte maturation

Positive and negative selection during lymphocyte maturation

REARRANGEMENT OF ANTIGEN RECEPTOR GENES IN B AND T LYMPHOCYTES

Germline organization of human Ig loci

Domains of Ig and TCR proteins [V(D)J Recombination]

Germline organization of human TCR loci

Diversity of antigen receptor genes

V(D)J recombination

Transcriptional regulation of Ig genes

Sequential events during V(D)J recombination

Junctional Diversity

B LYMPHOCYTE DEVELOPMENT

Stages of B cell Maturation

Ig heavy and light chain gene recombination and expression

Pre-B cell and pre-T cell receptors

B lymphocyte subsets

Co-expression of IgM and IgD

MATURATION OF T LYMPHOCYTES

Stages of T cell maturation

Maturation of T cells in the Thymus

TCR α and β chain gene recombination and expression

CD4 and CD8 expression on thymocytes and positive selection of T cells in the thymus

γδ T Lymphocytes In fetal thymuses, the first TCR gene rearrangements involve the γ and δ loci The diversity of the γδ T cell repertoire is theoretically even greater than that of the αβ T cell repertoire Paradoxically, however, the actual diversity of expressed γδ TCRs is limited because only a few of the available V, D, and J segments are used in mature γδ T cells, for unknown reasons