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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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Autores principales: Zheng, Junfeng, Huang, Qiaoniang, Huang, Renliang, Deng, Fengyuan, Yue, Xiaoyang, Yin, Junping, Zhao, Wenjie, Chen, Yan, Wen, Lifang, Zhou, Jun, Huang, Renda, Riemekasten, Gabriela, Liu, Zuguo, Petersen, Frank, Yu, Xinhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661054/
https://www.ncbi.nlm.nih.gov/pubmed/29118759
http://dx.doi.org/10.3389/fimmu.2017.01384
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author Zheng, Junfeng
Huang, Qiaoniang
Huang, Renliang
Deng, Fengyuan
Yue, Xiaoyang
Yin, Junping
Zhao, Wenjie
Chen, Yan
Wen, Lifang
Zhou, Jun
Huang, Renda
Riemekasten, Gabriela
Liu, Zuguo
Petersen, Frank
Yu, Xinhua
author_facet Zheng, Junfeng
Huang, Qiaoniang
Huang, Renliang
Deng, Fengyuan
Yue, Xiaoyang
Yin, Junping
Zhao, Wenjie
Chen, Yan
Wen, Lifang
Zhou, Jun
Huang, Renda
Riemekasten, Gabriela
Liu, Zuguo
Petersen, Frank
Yu, Xinhua
author_sort Zheng, Junfeng
collection PubMed
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 pubmed-56610542017-11-08 B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s Syndrome Zheng, Junfeng Huang, Qiaoniang Huang, Renliang Deng, Fengyuan Yue, Xiaoyang Yin, Junping Zhao, Wenjie Chen, Yan Wen, Lifang Zhou, Jun Huang, Renda Riemekasten, Gabriela Liu, Zuguo Petersen, Frank Yu, Xinhua Front Immunol Immunology 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. Frontiers Media S.A. 2017-10-24 /pmc/articles/PMC5661054/ /pubmed/29118759 http://dx.doi.org/10.3389/fimmu.2017.01384 Text en Copyright © 2017 Zheng, Huang, Huang, Deng, Yue, Yin, Zhao, Chen, Wen, Zhou, Huang, Riemekasten, Liu, Petersen and Yu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zheng, Junfeng
Huang, Qiaoniang
Huang, Renliang
Deng, Fengyuan
Yue, Xiaoyang
Yin, Junping
Zhao, Wenjie
Chen, Yan
Wen, Lifang
Zhou, Jun
Huang, Renda
Riemekasten, Gabriela
Liu, Zuguo
Petersen, Frank
Yu, Xinhua
B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren’s Syndrome
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 sjögren’s syndrome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661054/
https://www.ncbi.nlm.nih.gov/pubmed/29118759
http://dx.doi.org/10.3389/fimmu.2017.01384
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