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

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 c...

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Main Authors: 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-10-01
Series:Frontiers in Immunology
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Online Access:http://journal.frontiersin.org/article/10.3389/fimmu.2017.01384/full
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author Junfeng Zheng
Junfeng Zheng
Qiaoniang Huang
Renliang Huang
Fengyuan Deng
Xiaoyang Yue
Junping Yin
Wenjie Zhao
Yan Chen
Lifang Wen
Jun Zhou
Renda Huang
Gabriela Riemekasten
Gabriela Riemekasten
Zuguo Liu
Frank Petersen
Xinhua Yu
Xinhua Yu
author_facet Junfeng Zheng
Junfeng Zheng
Qiaoniang Huang
Renliang Huang
Fengyuan Deng
Xiaoyang Yue
Junping Yin
Wenjie Zhao
Yan Chen
Lifang Wen
Jun Zhou
Renda Huang
Gabriela Riemekasten
Gabriela Riemekasten
Zuguo Liu
Frank Petersen
Xinhua Yu
Xinhua Yu
author_sort Junfeng Zheng
collection DOAJ
description 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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spelling doaj.art-e7e059c0e5ee4a1eaee8f899cf57b03e2022-12-22T02:33:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01384303942B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s SyndromeJunfeng Zheng0Junfeng Zheng1Qiaoniang Huang2Renliang Huang3Fengyuan Deng4Xiaoyang Yue5Junping Yin6Wenjie Zhao7Yan Chen8Lifang Wen9Jun Zhou10Renda Huang11Gabriela Riemekasten12Gabriela Riemekasten13Zuguo Liu14Frank Petersen15Xinhua Yu16Xinhua Yu17Xiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaInstitute of Psychiatry and Neuroscience, Xinxiang Medical University, XinXiang, ChinaXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaPriority Area Asthma & Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, GermanyXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaInstitute of Psychiatry and Neuroscience, Xinxiang Medical University, XinXiang, ChinaDepartment of Rheumatology, University of Lübeck, Lübeck, GermanyEye Institute of Xiamen University, The Medical College of Xiamen University, Xiamen, ChinaPriority Area Asthma & Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, GermanyXiamen-Borstel Joint Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, ChinaPriority Area Asthma & Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, GermanyPrimary 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01384/fullprimary Sjögren’s syndromemouse modelT cell epitopeSSAautoantibodiesB cells
spellingShingle Junfeng Zheng
Junfeng Zheng
Qiaoniang Huang
Renliang Huang
Fengyuan Deng
Xiaoyang Yue
Junping Yin
Wenjie Zhao
Yan Chen
Lifang Wen
Jun Zhou
Renda Huang
Gabriela Riemekasten
Gabriela Riemekasten
Zuguo Liu
Frank Petersen
Xinhua Yu
Xinhua Yu
B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s Syndrome
Frontiers in Immunology
primary Sjögren’s syndrome
mouse model
T cell epitope
SSA
autoantibodies
B cells
title B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s Syndrome
title_full B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s Syndrome
title_fullStr B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s Syndrome
title_full_unstemmed B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s Syndrome
title_short B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s Syndrome
title_sort b cells are indispensable for a novel mouse model of primary sjogren s syndrome
topic primary Sjögren’s syndrome
mouse model
T cell epitope
SSA
autoantibodies
B cells
url http://journal.frontiersin.org/article/10.3389/fimmu.2017.01384/full
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