Yoshimoto Keiko, Takahashi Yasue, Ogasawara Mie, Setoyama Yumiko, Suzuki Katsuya, Tsuzaka Kensei, Abe Tohru, Takeuchi Tsutomu
Division of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama 350-8550, Japan.
Int Immunol. 2006 Jul;18(7):1189-96. doi: 10.1093/intimm/dxl053. Epub 2006 Jun 1.
B cell-activating factor of the tumor necrosis factor (TNF) family, or BAFF, is mainly produced in monocytes and dendritic cells, and indispensable for proliferation, differentiation and survival of B cells. BAFF is a type II membrane-bound protein and the extracellular C-terminal fragment is released from the cells as soluble BAFF (sBAFF), which binds to specific receptors on B cells. Accumulating evidence suggests that BAFF plays an important role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). In this study, we developed a sensitive sandwich ELISA system to quantify the amount of sBAFF using our own mAb. Treatment of peripheral T cells of SLE patients with an anti-CD3 antibody triggered robust expression of BAFF and subsequent release of sBAFF from the cells. On the other hand, the stimulus induced only marginal elevation of sBAFF from normal T cells. These data indicate that BAFF is expressed in T cells upon stimulation at least under pathological conditions. Expression of BAFF was also largely induced in a human T cell line, Loucy (American Type Tissue Collection CRL-2629), in response to several stimuli, while other T cell lines so far examined produced the cytokine almost constitutively. These data suggest that Loucy recapitulates some of the characteristics of SLE T cells. Investigation of molecular and cellular mechanisms of production of BAFF in Loucy demonstrated that expression of BAFF was regulated through a signal transduction pathway which involves c-jun NH2-terminal kinase and p38, and that shedding of BAFF was catalyzed by a membrane-bound protease, furin.
肿瘤坏死因子（TNF）家族的B细胞激活因子，即BAFF，主要在单核细胞和树突状细胞中产生，对B细胞的增殖、分化和存活不可或缺。BAFF是一种II型膜结合蛋白，其细胞外C末端片段以可溶性BAFF（sBAFF）的形式从细胞中释放出来，与B细胞上的特异性受体结合。越来越多的证据表明，BAFF在自身免疫性疾病（如系统性红斑狼疮，SLE）的发病机制中起重要作用。在本研究中，我们开发了一种灵敏的夹心ELISA系统，使用我们自己的单克隆抗体来定量sBAFF的量。用抗CD3抗体处理SLE患者的外周T细胞会引发BAFF的强烈表达以及随后sBAFF从细胞中的释放。另一方面，该刺激仅引起正常T细胞中sBAFF的少量升高。这些数据表明，至少在病理条件下，BAFF在刺激后在T细胞中表达。在人T细胞系Loucy（美国典型培养物保藏中心CRL-2629）中，对几种刺激的反应也大量诱导了BAFF的表达，而迄今为止检测的其他T细胞系几乎组成性地产生这种细胞因子。这些数据表明，Loucy概括了SLE T细胞的一些特征。对Loucy中BAFF产生的分子和细胞机制的研究表明，BAFF的表达通过涉及c-jun NH2末端激酶和p38的信号转导途径进行调节，并且BAFF的脱落由膜结合蛋白酶弗林蛋白酶催化。
