International Immunology Advance Access originally published online on June 1, 2006
International Immunology 2006 18(7):1189-1196; doi:10.1093/intimm/dxl053
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Aberrant expression of BAFF in T cells of systemic lupus erythematosus, which is recapitulated by a human T cell line, Loucy
1 Division of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama 350-8550, Japan
2 Research Park 6N9, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Correspondence to: K. Yoshimoto; E-mail: keiyoshi{at}sc.itc.keio.ac.jp
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.
Keywords: autoimmune disease, BAFF, furin, IFN-
, systemic lupus erythematosus, T cell
Transmitting editor: S. L. Swain
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