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Lymphocyte Development and Antigen Receptor Gene Rearrangement Chapter 8
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Stages of lymphocyte maturation
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Pluripotent stem cells give rise to distinct B and T lineages
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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
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Checkpoints in lymphocyte maturation
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Positive and negative selection during lymphocyte maturation
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REARRANGEMENT OF ANTIGEN RECEPTOR GENES IN B AND T LYMPHOCYTES
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Germline organization of human Ig loci
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Domains of Ig and TCR proteins [V(D)J Recombination]
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Germline organization of human TCR loci
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Diversity of antigen receptor genes
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V(D)J recombination
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Transcriptional regulation of Ig genes
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Sequential events during V(D)J recombination
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Junctional Diversity
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B LYMPHOCYTE DEVELOPMENT
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Stages of B cell Maturation
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Ig heavy and light chain gene recombination and expression
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Pre-B cell and pre-T cell receptors
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B lymphocyte subsets
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Co-expression of IgM and IgD
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MATURATION OF T LYMPHOCYTES
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Stages of T cell maturation
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Maturation of T cells in the Thymus
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TCR α and β chain gene recombination and expression
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CD4 and CD8 expression on thymocytes and positive selection of T cells in the thymus
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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
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