Transcript LYMPHOCYTE DEVELOPMENT and the REARRANGEMENT and

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