B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren's Syndrome

细胞对于原发性干燥综合征新型小鼠模型至关重要

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作者:Junfeng Zheng, Qiaoniang Huang, Renliang Huang, Fengyuan Deng, Xiaoyang Yue, Junping Yin, Wenjie Zhao, Yan Chen, Lifang Wen, Jun Zhou, Renda Huang, Gabriela Riemekasten, Zuguo Liu, Frank Petersen, Xinhua Yu

Abstract

Primary Sjögren's syndrome (pSS) is characterized by a panel of autoantibodies, while it is not clear whether B cells and autoantibodies play an essential role in pathogenesis of the disease. Here, we report a novel mouse model for pSS which is induced by immunization with the Ro60_316-335 peptide containing a predominant T cell epitope. After immunization, mice developed several symptoms mimicking pSS, including a decreased secretion of tears, lymphocytic infiltration into the lacrimal glands, autoantibodies, and increased levels of inflammatory cytokines. Disease susceptibility to this novel mouse model varies among strains, where C3H/HeJ (H2-k) and C3H/HeN (H2-k) are susceptible while DBA/1 (H2-q) and C57BL/6 (H2-b) are resistant. Depletion of B cells using anti-CD20 monoclonal antibodies prevented C3H/HeN mice from development of the pSS-like disease. In addition, HLA-DRB1*0803, a pSS risk allele, was predicted to bind to the hRo60_308-328 which contains a predominant T cell epitope of human Ro60. Therefore, this study provides a novel mouse model for pSS and reveals an indispensable role of B cells in this model. Moreover, it suggests that T cell epitope within Ro60 antigen is potentially pathogenic for pSS.

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