Regulation of immunoglobulin heavy-chain gene rearrangements

Immunological Reviews
Dipanjan Chowdhury, Ranjan Sen

Abstract

Regulated assembly of antigen receptor gene segments to produce functional genes is a hallmark of B- and T-lymphocyte development. The immunoglobulin heavy-chain (IgH) and T-cell receptor beta-chain genes rearrange first in B and T lineages, respectively. Both loci require two recombination events to assemble functional genes; D-to-J recombination occurs first followed by V-to-DJ recombination. Despite similarities in overall rearrangement patterns, each locus has unique regulatory features. Here, we review the characteristics of IgH gene rearrangements such as developmental timing, deletion versus inversion, DH gene segment utilization, ordered recombination of VH gene segments, and feedback inhibition of rearrangement in pre-B cells. We summarize chromatin structural features of the locus before and during recombination and, wherever possible, incorporate these into working hypotheses for understanding regulation of IgH gene recombination. The picture emerges that the IgH locus is activated in discrete, independently regulated domains. A domain encompassing DH and JH gene segments is activated first, within which recombination is initiated. VH genes are activated subsequently and, in part, by interleukin-7. These observations...Continue Reading

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Citations

Oct 5, 2010·Archivum Immunologiae Et Therapiae Experimentalis·Michael L SikesJustin M Bradshaw
May 17, 2007·Genes & Development·Huifei LiuYang Shi
May 10, 2005·Immunology and Cell Biology·Dipanjan Chowdhury, Carl D Novina
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Sep 25, 2010·Seminars in Immunology·Ramesh Subrahmanyam, Ranjan Sen
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