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

Dennis M. Willerford, Wojciech Swat, Frederick W. Alt

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

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.

Original languageEnglish
Pages (from-to)603-609
Number of pages7
JournalCurrent Opinion in Genetics and Development
Volume6
Issue number5
DOIs
StatePublished - Oct 1996
Externally publishedYes

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