Regulation of Vβ germline transcription in RAG-deficient mice by the CD3ε-mediated signals:: implication of Vβ transcriptional regulation in TCR β allelic exclusion

During the thymic development of ap lineage T cells, maturation of the CD4(-)CD8(-) double-negative (DN) cells into the CD4(+)CD8(+) double-positive cells is accompanied by the induction of TCR beta allelic exclusion. Recent studies have shown that these events are regulated by the signals through the pre-TCR complex which consists of the TCR beta, pre-TCR alpha and CD3 components. The V-beta germline transcripts are detected prior to the TCR beta chain gene rearrangements in the DN thymocytes. To examine the effects of the pre-TCR-mediated signals on V-beta germline transcription, we analyzed thymocytes from RAG-2-deficient mice treated with anti-CD3 epsilon antibody. The germline transcripts of all V-beta we examined, except for V(beta)14, were down-regulated by the anti-CD3 epsilon antibody treatment. These data indicate that the regulation of V-beta germline transcription by the signals through the pre-TCR complex may reflect the modulation of V-beta accessibility to the VDJ recombinase, which contributes to TCR beta allelic exclusion.