Orbital fibroblasts of Graves' orbitopathy stimulated with proinflammatory cytokines promote B cell survival by secreting BAFF

Publication date: 5 May 2017
Source:Molecular and Cellular Endocrinology, Volume 446
Author(s): Fen Tang, Xiaoqing Chen, Yuxiang Mao, Shangtao Wan, Siming Ai, Huasheng Yang, Guangming Liu, Yusha Zou, Miaoli Lin, Liang Dan
The success of rituximab for the treatment of active Graves' orbitopathy (GO) suggests that B cells play a critical role in intraorbital inflammation. B cell activating factor (BAFF) and its homolog a proliferation-inducing ligand (APRIL) are critical for B cell survival. However, the contribution of BAFF/APRIL to GO remains unclear. We sought to determine the role of BAFF/APRIL in the orbits of GO, and found that BAFF was markedly upregulated, while APRIL was not. Additionally, cultured GO orbital fibroblasts (GO-OFs)² expressing BAFF were induced to produce a large amount of BAFF. In contrast, a weak APRIL expression was detected in the OFs, and they exhibited a slight response to stimulation. Notably, pretreated GO-OFs promoted B cell survival, and this effect was significantly inhibited by a BAFF-R neutralizing antibody. This study indicates that OFs from GO can express BAFF and mediate the intraorbital survival of B cells via BAFF mechanism.



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