Cutting Edge: BAFF Promotes Autoantibody Production via TACI-Dependent Activation of Transitional B Cells.
Cutting Edge: BAFF Promotes Autoantibody Production via TACI-Dependent Activation of Transitional B Cells.
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尖端：BAFF通过过渡B细胞的TACI依赖性激活促进自身抗体的产生。
DOI：
10.4049/jimmunol.1600017
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发表时间：
2016-05-01
期刊：
影响因子：
--
通讯作者：
Jackson SW
中科院分区：
文献类型：
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作者：
Jacobs HM;Thouvenel CD;Leach S;Arkatkar T;Metzler G;Scharping NE;Kolhatkar NS;Rawlings DJ;Jackson SW
过表达TNF家族B细胞活化因子（BAFF）的小鼠产生以类别转换的抗核抗体为特征的全身性自身免疫。跨膜激活因子和CAML相互作用因子（TACI）信号对BAFF介导的自身免疫至关重要，但在过量BAFF的环境中经历TACI依赖性激活的B细胞发育亚群仍不清楚。我们现在报道，尽管表面TACI表达通常仅限于成熟B细胞，但过量的BAFF促进表达TACI的过渡型B细胞的扩增。来自BAFF-Tg小鼠的TACIhi移行细胞的特征在于活化的循环表型;并且TACIhi细胞亚群特异性富集自身反应性，表达活化诱导的胞苷脱氨酶（AID）和T-bet，并表现出体细胞超突变的证据。与BAFF介导的体液自身免疫的潜在贡献一致，来自BAFF-Tg小鼠的TACIhi过渡B细胞自发地离体产生类别转换的自身抗体。这些综合研究结果强调了一种新的机制，BAFF通过直接的TACI依赖性激活过渡期B细胞来促进体液自身免疫。
Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear antibodies. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remains unclear. We now report that, whereas surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACIhi transitional cells from BAFF-Tg mice are characterized by an activated, cycling phenotype; and the TACIhi cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase (AID) and T-bet and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACIhi transitional B cells from BAFF-Tg mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism whereby BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells.