title: Orbital fibroblasts of Graves' orbitopathy stimulated with proinflammatory cytokines promote B cell survival by secreting BAFF.
abstract: 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)2expressing 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.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
authors.forename: Fen
authors.initials: F
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
authors.forename: Shangtao
authors.initials: S
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
authors.forename: Siming
authors.initials: S
authors.lastname: Ai
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
authors.forename: Huasheng
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China.
authors.forename: Yusha
authors.initials: Y
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China. Electronic address: 1019213902@qq.com.
authors.forename: Miaoli
authors.initials: M
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China. Electronic address: liangd2@mail.sysu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Dan
mesh_terms: D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D049970:Graves Ophthalmopathy / Q000473:pathology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053264:B-Cell Activating Factor; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: A proliferation-inducing ligand (APRIL); B-cell activating factor (BAFF); Graves' orbitopathy; Orbital fibroblasts