Regulation of antigen receptor gene assembly in lymphocytes

E. M. Oltz

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Somatic alterations affecting the mammalian genome occur exclusively in B and T cells. Developing lymphocytes employ a series of DNA recombination events (V(D)J recombination) to assemble a diverse repertoire of immunoglobulin (Ig) and T cell receptor (TCR) variable regions from a large array of germline gene segments. V(D)J recombination is required not only for receptor diversification but also for lymphocyte development. At a molecular level, these recombination events are directed by conserved DNA sequences flanking all antigen receptor gene segments that function as recognition signals for a single recombinase activity. Despite these shared features, recombination events are controlled at the levels of stage- and tissue-specificity. Our primary research focus is to dissect the mechanisms that regulate assembly of antigen receptor loci by rendering certain gene segments accessible to a common V(D)J recombinase. This article discusses recent discoveries from the author's laboratory that address this long-standing issue. We have found that transcriptional promoters are critical cis-acting regulatory elements for targeting efficient recombination of chromosomal gene segments. We have also demonstrated that activation of NF-κB signaling in precursor B cells is required for global regulation of Ig light chain gene assembly. Together, these findings provide key insights into the genetic mechanisms that regulate antigen receptor diversity and the developmental pathways leading to the acquisition of lymphocyte effector function.

Original languageEnglish
Pages (from-to)121-133
Number of pages13
JournalImmunologic Research
Volume23
Issue number2-3
DOIs
StatePublished - Jul 5 2001

Keywords

  • Gene Regulation
  • Immunoglobulins
  • T Cell Receptors
  • Transcription Factors
  • V(D)J Recombination

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