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 αβ lineage T cells, maturation of the CD4-CD8- double-negative (DN) cells into the CD4+CD8+ double-positive cells is accompanied by induction of TCR β allelic exclusion. Recent studies have shown that these events are regulated by the signals through the pre-TCR complex which consists of the TCR β, pre-TCR α and CD3 components. The Vβ germline transcripts are detected prior to the TCR β chain gene rearrangements in the DN thymocytes. To examine the effects of the pre-TCR-mediated signals on Vβ germline transcription, we analyzed thymocytes from TAG-2-deficient mice treated with anti-CD3ε antibody. The germline transcripts of all Vβ we examined, except for Vβ14, were down-regulated by the anti-CD3ε antibody treatment. These data indicate that the regulation of Vβ germline transcription by the signals through the pre-TCR complex may reflect the modulation of Vβ accessibility to the VDJ recombinase, which contributes to TCR β allelic exclusion. [ABSTRACT FROM PUBLISHER]