Regulation of Vbeta germline transcription in RAG-deficient mice by the CD3epsilon-mediated signals: implication of Vbeta transcriptional regulation in TCR beta allelic exclusion

Abstract

During the thymic development of alphabeta 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 Vbeta 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 Vbeta germline transcription, we analyzed thymocytes from RAG-2-deficient mice treated with anti-CD3epsilon antibody. The germline transcripts of all Vbeta we examined, except for Vbeta14, were down-regulated by the anti-CD3epsilon antibody treatment. These data indicate that the regulation of Vbeta germline transcription by the signals through the pre-TCR complex may reflect the modulation of Vbeta accessibility to the VDJ recombinase, which contributes to TCR beta allelic exclusion.