Developmental regulation of V(D)J recombination and lymphocyte differentiation.
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.
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Howard Hughes Medical Institute, The Children's Hospital, Boston, Massachusetts 02115, USA. dwiller@u.washington.edu
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D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D004254:DNA Nucleotidyltransferases / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008954:Models, Biological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D045567:VDJ Recombinases
D016693:Receptors, Antigen, T-Cell, alpha-beta; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases