Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells.
Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells.
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DOI：
10.1084/jem.188.4.765
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发表时间：
1998-08-17
期刊：
影响因子：
--
通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
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作者：
Meffre E;Papavasiliou F;Cohen P;de Bouteiller O;Bell D;Karasuyama H;Schiff C;Banchereau J;Liu YJ;Nussenzweig MC
生发中心是位于外周淋巴器官中的一个解剖隔室，B细胞在这里进行克隆扩增、体细胞突变、开关重组和免疫球蛋白基因V(D)J重组。由于体细胞突变，一些GC B细胞产生亲和力更高的抗体，而另一些细胞发生突变，亲和力降低，还有一些细胞可能会产生自我反应。有研究认为，GC中的二次V(D)J重排可能会挽救受体因体细胞突变而受损的B细胞。在这里，我们提出的证据表明，成熟的人扁桃体B细胞共表达传统的轻链和重组相关基因，并当它们的受体交联时，它们消除了重组激活基因和末端脱氧核苷酸转移酶的表达。因此，重组酶对外周B细胞受体结合的反应与发育中的B细胞对相同刺激的反应相反。这些观察表明，受体修正是受体多样化的一种机制，当抗原受体被同源抗原交叉连接时，该机制被关闭。
The germinal center (GC) is an anatomic compartment found in peripheral lymphoid organs, wherein B cells undergo clonal expansion, somatic mutation, switch recombination, and reactivate immunoglobulin gene V(D)J recombination. As a result of somatic mutation, some GC B cells develop higher affinity antibodies, whereas others suffer mutations that decrease affinity, and still others may become self-reactive. It has been proposed that secondary V(D)J rearrangements in GCs might rescue B cells whose receptors are damaged by somatic mutations. Here we present evidence that mature human tonsil B cells coexpress conventional light chains and recombination associated genes, and that they extinguish recombination activating gene and terminal deoxynucleotidyl transferase expression when their receptors are cross-linked. Thus, the response of the recombinase to receptor engagement in peripheral B cells is the opposite of the response in developing B cells to the same stimulus. These observations suggest that receptor revision is a mechanism for receptor diversification that is turned off when antigen receptors are cross-linked by the cognate antigen.