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