Control of V(D)J recombinational accessibility of the D beta 1 gene segment at the TCR beta locus by a germline promoter

Immunity. 1999 Mar;10(3):313-22. doi: 10.1016/s1074-7613(00)80031-x.

Abstract

The germline promoter region upstream of the D beta 1 gene segment in the murine TCR beta locus was deleted to assess its role in controlling V(D)J recombination. Associated with diminished D beta 1 region germline transcription, rearrangement of the D beta 1 but not the D beta 2 gene segment was reduced 10- to 20-fold. A corresponding reduction in RAG-mediated cleavage at the D beta 1 and J beta 1 signal sequences was apparent only when purified CD4- CD8- thymocytes were analyzed because, as we demonstrate, cleavage at these gene segments also occurred in CD4+ CD8+ thymocytes. These findings suggest that germline promoters regulate localized accessibility of gene segments for recombination and that in CD4+ CD8+ thymocytes TCR beta allelic exclusion does not result from inaccessibility of D beta gene segments.

Publication types

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

MeSH terms

  • Animals
  • Gene Deletion
  • Gene Rearrangement, T-Lymphocyte / genetics*
  • Gene Rearrangement, T-Lymphocyte / immunology
  • Gene Targeting
  • Genes, T-Cell Receptor beta / genetics
  • Genes, T-Cell Receptor beta / immunology*
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Promoter Regions, Genetic / immunology*
  • Recombination, Genetic / immunology*
  • Transcription, Genetic / immunology