Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter
Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter
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DOI：
10.1016/s1074-7613(00)80029-1
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发表时间：
1999-03-01
期刊：
影响因子：
32.4
通讯作者：
Monroe, JG
中科院分区：
文献类型：
--
作者：
Sandel, PC;Monroe, JG
遇到自身抗原的未成熟B细胞通过阴性选择从免疫库中消除。已经提出负选择通过两种不同的机制发生：通过细胞凋亡的缺失或通过受体编辑改变抗原受体特异性。虽然每一种模式都有令人信服的证据，但这两种模式本质上是矛盾的。在本文中，我们提出了一个解决这个矛盾的方法，证明第一次接触抗原的位点决定了使用哪种负选择机制。我们证明，骨髓微环境提供的信号，阻止抗原诱导的缺失，促进RAG再诱导。在外周，这些信号的缺乏使得未成熟的B细胞由于BCR接合而默认凋亡。
Immature B cells that encounter self-antigen are eliminated from the immune repertoire by negative selection. Negative selection has been proposed to take place by two distinct mechanisms: deletion by apoptosis or alteration of the antigen receptor specificity by receptor editing. While convincing evidence exists for each, the two models are inherently contradictory. In this paper, we propose a resolution to this contradiction by demonstrating that the site of first antigen encounter dictates which mechanism of negative selection is utilized. We demonstrate that the bone marrow microenvironment provides signals that block antigen-induced deletion and promote RAG reinduction. In the periphery, the absence of these signals allows the immature B cell to default to apoptosis as a result of BCR engagement.