B cells take the front seat: dysregulated B cell signals orchestrate loss of tolerance and autoantibody production.

B cells take the front seat: dysregulated B cell signals orchestrate loss of tolerance and autoantibody production.
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DOI:
10.1016/j.coi.2015.01.018
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发表时间:
2015-04
影响因子:
7
通讯作者:
Rawlings, David J.
Rawlings, David J.
中科院分区:
医学2区
文献类型:
--
作者:
Jackson, Shaun W.;Kolhatkar, Nikita S.;Rawlings, David J.

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A significant proportion of autoimmune-associated genetic variants are expressed in B cells, suggesting that B cells may play multiple roles in autoimmune pathogenesis. In this review, we highlight recent studies demonstrating that even modest alterations in B cell signaling are sufficient to promote autoimmunity. First, we describe several examples of genetic variations promoting B cell-intrinsic initiation of autoimmune germinal centers and autoantibody production. We highlight how dual antigen receptor/toll-like receptor signals greatly facilitate this process and how activated, self-reactive B cells may function as antigen presenting cells, leading to loss of T cell tolerance. Further, we propose that B cell-derived cytokines may initiate and/or sustain autoimmune germinal centers, likely also contributing, in parallel, to programing of self-reactive T cells.
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