Altered B cell signalling in autoimmunity.

Altered B cell signalling in autoimmunity.
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DOI:
10.1038/nri.2017.24
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发表时间:
2017-07
期刊:
Nature reviews. Immunology
影响因子:
--
通讯作者:
Jackson SW
Jackson SW
中科院分区:
其他
文献类型:
--
作者:
Rawlings DJ;Metzler G;Wray-Dutra M;Jackson SW

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最近的工作提供了新的见解,如何改变B细胞的内在信号-通过B细胞受体(BCR)和关键的辅助受体-共同发挥作用,以促进自身免疫的发病机制。这些组合的信号在两个不同的阶段影响B细胞:第一,在幼稚库的选择;第二,在滤泡外或生发中心激活反应。因此,失调的信号传导可以导致改变的幼稚BCR库和产生自身抗体的B细胞。引人注目的是,高亲和力自身抗体可以预测和预测一些自身免疫性疾病,包括1型糖尿病和系统性红斑狼疮。这篇综述总结了如何,而不是自身反应性T细胞活化的下游后果,失调的B细胞信号可以作为许多人类自身免疫性疾病的主要驱动程序。
Recent work has provided new insights into how altered B cell-intrinsic signals — through the B cell receptor (BCR) and key co-receptors — function together to promote the pathogenesis of autoimmunity. These combined signals affect B cells at two distinct stages: first, in the selection of the naive repertoire; and second, during extrafollicular or germinal centre activation responses. Thus, dysregulated signalling can lead to both an altered naive BCR repertoire and the generation of autoantibody-producing B cells. Strikingly, high-affinity autoantibodies predate and predict disease in several autoimmune disorders, including type 1 diabetes and systemic lupus erythematosus. This Review summarizes how, rather than being a downstream consequence of autoreactive T cell activation, dysregulated B cell signalling can function as a primary driver of many human autoimmune diseases.
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