Tang Fen, Chen Xiaoqing, Mao Yuxiang, Wan Shangtao, Ai Siming, Yang Huasheng, Liu Guangming, Zou Yusha, Lin Miaoli, Dan Liang
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
Mol Cell Endocrinol. 2017 May 5;446:1-11. doi: 10.1016/j.mce.2017.01.014. Epub 2017 Jan 10.
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) 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.
利妥昔单抗治疗活动性格雷夫斯眼眶病（GO）的成功表明，B细胞在眶内炎症中起关键作用。B细胞活化因子（BAFF）及其同源物增殖诱导配体（APRIL）对B细胞存活至关重要。然而，BAFF/APRIL对GO的作用仍不清楚。我们试图确定BAFF/APRIL在GO眼眶中的作用，发现BAFF明显上调，而APRIL没有。此外，表达BAFF的培养GO眼眶成纤维细胞（GO-OFs）被诱导产生大量BAFF。相比之下，在成纤维细胞中检测到较弱的APRIL表达，并且它们对刺激表现出轻微反应。值得注意的是，预处理的GO-OFs促进了B细胞存活，并且这种作用被BAFF-R中和抗体显著抑制。这项研究表明，来自GO的成纤维细胞可以表达BAFF，并通过BAFF机制介导B细胞在眶内的存活。
