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Transcript
Chapter 8 Lymphocyte Development and Antigen Receptor Gene Rearrangement 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
