Editing anti-DNA B cells by Vlambdax.

Editing anti-DNA B cells by Vlambdax.
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通过VlambDax编辑抗DNA B细胞。

DOI:
10.1084/jem.20031712
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发表时间:
2004-02-02
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Weigert M
Weigert M
中科院分区:
其他
文献类型:
--
作者:
Li Y;Louzoun Y;Weigert M

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受体编辑是通过替换有助于自身反应的Vκ基因来执行的。此外,Cκ基因座可通过Vκ重排为内含子或3‘的CκRS序列(也称为κ缺失元件)来删除。删除Cκ的B细胞可以表达λ轻链。然而,λ基因座,无论是人还是老鼠,都不允许V基因替换。它似乎也没有被删除。因此,编辑自身反应性λB细胞可能需要其他途径。我们发现,在抗DNA重链转基因小鼠VH3H9/56R中,表达由λ1组成的抗DNA受体与抗DNA重链相关的B细胞通常共表达一条阻止κ结合的DNA链。我们推测,这种同型包涵体细胞可能具有较低的抗DNA受体密度,这一特征可能导致自我耐受。在这里,我们描述了一种通过表达Vλ家族中很少使用的成员Vλx来阻止DNA结合的机制。λx B细胞也表达CD25,可能代表已经用尽了轻链编辑可能性的B细胞。
Receptor editing is performed by replacement of Vκ genes that contribute to autoreactivity. In addition, the Cκ locus can be deleted by Vκ rearrangement to intronic or 3′ of Cκ RS sequences (also referred to as κ deletion elements). B cells that delete the Cκ can then express λ light chains. However, the λ locus, either of man or mouse, does not allow V gene replacement. Nor does it appear to be deleted. Therefore, editing of autoreactive λ B cells may require alternative pathways. We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of λ1 in association with an anti-DNA heavy chain often coexpress a κ chain that prevents DNA binding. We speculate that such isotypically included cells may have low anti-DNA receptor densities, a feature that may lead to self-tolerance. Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the Vλ family, Vλx. The λx B cells of the tgs also express CD25 and may represent B cells that have exhausted light chain editing possibilities.
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