B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren's Syndrome.
B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren's Syndrome.
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B 细胞对于原发性干燥综合征的新型小鼠模型是不可或缺的
DOI：
10.3389/fimmu.2017.01384
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发表时间：
2017
影响因子：
7.3
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Zheng J;Huang Q;Huang R;Deng F;Yue X;Yin J;Zhao W;Chen Y;Wen L;Zhou J;Huang R;Riemekasten G;Liu Z;Petersen F;Yu X
原发性Sjögren综合征（pSS）以自身抗体组为特征，而B细胞和自身抗体是否在该疾病的发病机制中起重要作用尚不清楚。在这里，我们报道了一种新的小鼠pSS模型，该模型是通过含有主要T细胞表位的Ro60_316-335肽免疫诱导的。免疫后，小鼠出现了几种类似pSS的症状，包括眼泪分泌减少、淋巴细胞渗入泪腺、自身抗体和炎症细胞因子水平升高。不同菌株对这种新型小鼠模型的疾病易感性不同，其中C3H/HeJ （H2-k）和C3H/HeN （H2-k）易感，DBA/1 （H2-q）和C57BL/6 （H2-b）耐药。使用抗cd20单克隆抗体消耗B细胞可阻止C3H/HeN小鼠发生pss样疾病。此外，预测pSS风险等位基因HLA-DRB1*0803与hRo60_308-328结合，hRo60_308-328含有人类Ro60的显性T细胞表位。因此，本研究提供了一种新的小鼠pSS模型，并揭示了B细胞在该模型中不可或缺的作用。提示Ro60抗原内的T细胞表位对pSS具有潜在致病作用。
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.