B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell-independent antibody formation
B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell-independent antibody formation
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DOI：
10.4049/jimmunol.173.4.2331
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发表时间：
2004-08-15
影响因子：
4.4
通讯作者：
Scott, ML
中科院分区：
文献类型：
--
作者：
Shulga-Morskaya, S;Dobles, M;Scott, ML
TNF相关配体，即属于TNF家族的B细胞活化因子（BAFF），是正常B细胞发育和存活所必需的，并且特异性结合受体跨膜活化剂和钙调节剂和亲环蛋白配体相互作用物（TACI）、B细胞成熟Ag（BCMA）和BAFF-R。完全缺乏BAFF的小鼠和表达天然突变形式的BAFF-R的A/WySnJ品系小鼠之间的相似性表明，BAFF主要通过BAFF-R起作用。然而，A/WySnJ小鼠表达的几乎全长的BAFF-R蛋白使得不可能明确解释这些动物中的受体功能。使用同源重组，我们创建了完全缺乏BAFF-R的小鼠，并将它们直接与A/WySnJ小鼠和缺乏BAFF的小鼠进行比较。BAFF-R-null小鼠表现出与BAFF（-/-）和A/WySnJ小鼠中观察到的相似的成熟B细胞损失。此外，缺乏TACI和BCMA的小鼠同时没有表现出B细胞损失，从而证实BAFF-R是传递BAFF依赖性B细胞存活信号的主要受体。然而，虽然BAFF-R-null小鼠不能进行T细胞依赖性Ab形成，但它们与BAFF缺陷小鼠在产生正常水平的Ab至至少一些T细胞非依赖性Ag方面不同。这些研究清楚地表明，除了BAFF-R，BAFF还通过受体在体内调节Ab应答。
The TNF-related ligand, B cell-activating factor belonging to the TNF family (BAFF), is necessary for normal B cell development and survival, and specifically binds the receptors transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), B cell maturation Ag (BCMA), and BAFF-R. Similarities between mice completely lacking BAFF and A/WySnJ strain mice that express a naturally occurring mutant form of BAFF-R suggest that BAFF acts primarily through BAFF-R. However, the nearly full-length BAFF-R protein expressed by A/WySnJ mice makes unambiguous interpretation of receptor function in these animals impossible. Using homologous recombination we created mice completely lacking BAFF-R and compared them directly to A/WySnJ mice and to mice lacking BAFF. BAFF-R-null mice exhibit loss of mature B cells similar to that observed in BAFF(-/-) and A/WySnJ mice. Also, mice lacking both TACI and BCMA simultaneously exhibit no B cell loss, thus confirming that BAFF-R is the primary receptor for transmitting the BAFF-dependent B cell survival signal. However, while BAFF-R-null mice cannot carry out T cell-dependent Ab formation, they differ from BAFF-deficient mice in generating normal levels of Ab to at least some T cell-independent Ags. These studies clearly demonstrate that BAFF regulates Ab responses in vivo through receptors in addition to BAFF-R.