The TACI Receptor Regulates T-Cell-Independent Marginal Zone B Cell Responses through Innate Activation-Induced Cell Death
The TACI Receptor Regulates T-Cell-Independent Marginal Zone B Cell Responses through Innate Activation-Induced Cell Death
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DOI：
10.1016/j.immuni.2013.05.019
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发表时间：
2013-09-19
期刊：
影响因子：
32.4
通讯作者：
Mackay, Fabienne
中科院分区：
文献类型：
--
作者：
Figgett, William A.;Fairfax, Kirsten;Mackay, Fabienne
激活诱导的细胞死亡（AICD）在免疫稳态和耐受中起着关键作用。在T细胞依赖性体液应答中，B细胞的AICD由T细胞上的Fas配体（FasL）启动，刺激B细胞上的Fas受体。相反，T细胞非依赖性B细胞反应涉及先天型B淋巴细胞，例如边缘区（MZ）B细胞，并且对先天B细胞对Toll样受体（TLR）激活的反应过程中控制AICD的机制知之甚少。在这里，我们表明，MZ B细胞进行AICD在体内TLR4激活的反应。跨膜激活因子、钙调节因子和亲环素配体相互作用因子（TACI）受体和TLR 4协同上调MZ B细胞上的FasL和Fas的表达，并且还抑制Fas诱导的凋亡信号传导的抑制剂。这些发现证明了TACI及其配体在T细胞非依赖性B细胞应答过程中调节AICD的未被认识的作用。
Activation-induced cell death (AICD) plays a critical role in immune homeostasis and tolerance. In T-cell-dependent humoral responses, AICD of B cells is initiated by Fas ligand (FasL) on T cells, stimulating the Fas receptor on B cells. In contrast, T-cell-independent B cell responses involve innate-type B lymphocytes, such as marginal zone (MZ) B cells, and little is known about the mechanisms that control AICD during innate B cell responses to Toll-like receptor (TLR) activation. Here, we show that MZ B cells undergo AICD in response to TLR4 activation in vivo. The transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) receptor and TLR4 cooperate to upregulate expression of both FasL and Fas on MZ B cells and also to repress inhibitors of Fas-induced apoptosis signaling. These findings demonstrate an unappreciated role for TACI and its ligands in the regulation of AICD during T-cell-independent B cell responses.