Developmental regulation of V(D)J recombination and lymphocyte differentiation

Curr Opin Genet Dev. 1996 Oct;6(5):603-9. doi: 10.1016/s0959-437x(96)80090-6.

Abstract

Recent insights into the mechanism of V(D)J recombination have clarified the direct role of the products of the recombination-activating genes Rag-1 and Rag-2 in site-specific DNA cleavage at recombination signal sequences and have identified components of the general DNA double-strand break repair pathway that participate in the rejoining of the Rag-1 and Rag-2-cut receptor gene segments. The V(D)J reaction is restricted to particular antigen receptor loci in a lineage-specific and stage-specific manner. This specificity appears to involve cis-regulatory elements, some of which also regulate transcription of the germline antigen receptor loci. Early developmental steps in the T and B lineages - including phenotypic differentiation, expansion of precursors, and selection processes - are effected in a stepwise fashion by signals generated, at least in part, by the products of the functionally rearranged antigen receptor genes themselves.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • DNA Nucleotidyltransferases / biosynthesis*
  • Gene Expression Regulation, Developmental*
  • Gene Rearrangement, T-Lymphocyte
  • Humans
  • Lymphocytes / cytology*
  • Lymphocytes / immunology*
  • Mice
  • Models, Biological
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • VDJ Recombinases

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • DNA Nucleotidyltransferases
  • VDJ Recombinases