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

Regulation of Vβ germline transcription in RAG-deficient mice by the CD3ε-mediated signals:: implication of Vβ transcriptional regulation in TCR β allelic exclusion
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DOI:
10.1093/intimm/10.5.553
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发表时间:
1998-05-01
影响因子:
4.4
通讯作者:
Shinkai, Y
Shinkai, Y
中科院分区:
医学3区
文献类型:
--
作者:
Senoo, M;Shinkai, Y

文献摘要

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在ap谱系T细胞的胸腺发育过程中,CD 4(-)CD 8(-)双阴性(DN)细胞成熟为CD 4(+)CD 8(+)双阳性细胞伴随着TCR β等位基因排斥的诱导。最近的研究表明,这些事件是由通过前TCR复合物的信号调节的,前TCR复合物由TCR β、前TCR α和CD 3组分组成。在DN胸腺细胞中TCR β链基因重排之前检测到V-β生殖系转录物。为了检测前TCR介导的信号对V-β生殖系转录的影响,我们分析了用抗CD 3 β抗体处理的RAG-2缺陷小鼠的胸腺细胞。我们检测的所有V-β的生殖系转录物,除了V(β)14,都被抗CD 3 β抗体处理下调。这些数据表明,通过前TCR复合物的信号对V-β种系转录的调节可能反映了V-β对VDJ重组酶的可接近性的调节,这有助于TCR β等位基因排斥。
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.