TACI, an enigmatic BAFF/APRIL receptor, with new unappreciated biochemical and biological properties
TACI, an enigmatic BAFF/APRIL receptor, with new unappreciated biochemical and biological properties
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DOI：
10.1016/j.cytogfr.2008.04.006
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发表时间：
2008-06-01
影响因子：
13
通讯作者：
Schneider, Pascal
中科院分区：
文献类型：
--
作者：
Mackay, Fabienne;Schneider, Pascal
BAFF是一种B细胞存活因子，与三种受体BAFF-R、TACI和BCMA结合。BAFF-R是触发幼稚B细胞存活和成熟的受体，而BCMA支持骨髓中浆细胞的存活。过多的BAFF产生导致自身免疫，推测是自身反应性B细胞不适当存活的结果。TACI的功能更加难以捉摸，TACI（-/-）小鼠揭示了该受体的两侧，阳性受体驱动T细胞非依赖性免疫反应，而阴性受体下调B细胞活化和扩增。最近的研究表明，TACI表达的调节与B细胞上先天受体的活化密切相关，并且响应于多聚体BAFF和APRIL的TACI信号传导向浆母细胞提供阳性信号。TACI如何负调节B细胞仍然难以捉摸，但可能涉及间接控制BAFF水平。与人类常见可变免疫缺陷（CVID）相关的TACI突变的发现不仅加强了其在体液应答中的重要作用，而且还表明了比最初从基因敲除动物中预期的更复杂的作用。TACI是一种不寻常的TNF受体样分子，具有复杂的作用模式。(c)2008爱思唯尔有限公司保留所有权利。
BAFF is a B cell survival factor that binds to three receptors BAFF-R, TACI and BCMA. BAFF-R is the receptor triggering naive B cell survival and maturation while BCMA supports the survival of plasma cells in the bone marrow. Excessive BAFF production leads to autoimmunity, presumably as the consequence of inappropriate survival of self-reactive B cells. The function of TACI has been more elusive with TACI(-/-) mice revealing two sides of this receptor, a positive one driving T cell-independent immune responses and a negative one down-regulating B cell activation and expansion. Recent work has revealed that the regulation of TACI expression is intimately linked to the activation of innate receptors on B cells and that TACI signalling in response to multimeric BAFF and APRIL provides positive signals to plasmablasts. How TACI negatively regulates B cells remains elusive but may involve an indirect control of BAFF levels. The discovery of TACI mutations associated with common variable immunodeficiency (CVID) in humans not only reinforces its important role for humoral responses but also suggests a more complex role than first anticipated from knockout animals. TACI is emerging as an unusual TNF receptor-like molecule with a sophisticated mode of action. (c) 2008 Elsevier Ltd. All rights reserved.