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

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.