Regulation of immunoglobulin heavy-chain gene rearrangements

Dipanjan Chowdhury, Ranjan Sen

Research output: Contribution to journalArticlepeer-review

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 β-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 lead to a model for feedback inhibition of IgH rearrangements.

Original languageEnglish (US)
Pages (from-to)182-196
Number of pages15
JournalImmunological Reviews
Volume200
DOIs
StatePublished - Aug 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Regulation of immunoglobulin heavy-chain gene rearrangements'. Together they form a unique fingerprint.

Cite this