Enhancement of T Follicular Helper Cell-Mediated Humoral Immunity Reponses During Development of Experimental Autoimmune Myasthenia Gravis

作     者：Ying-Zhe Cui Si-Ying Qu Lu-Lu Chang Jia-Rui Zhao Lili Mu Bo Sun Hu-Lun Li Tong-Shuai Zhang Guang-You Wang Qing-Fei Kong 

作者机构：Department of Neurobiology Heilongjiang Provincial Key Laboratory of Neurobiology Harbin Medical University 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2019年第35卷第3期

页      面：507-518页

核心收录：

学科分类：10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81000536,81471227,31371079,31671112 and 81430035) the China Postdoctoral Science Foundation(20100471094) the Returned Overseas Scholars Foundation of the Natural Science Foundation of Heilongjiang Province,China(LC2015029,QC2015022) the Science and Technology Research Project of the Education Department of Heilongjiang Province,China(12541z008) the Heilongjiang Province Postdoctoral Science Foundation(LBH-Q131111) the Open Topic of Key Laboratory of Neurobiology,General Colleges and Universities in Heilongjiang Province,China(2013HLJKLNT-05) 

主　　题：Follicular helper T cells Experimental autoimmune myasthenia gravis Acetylcholine receptor Germinal center 

摘      要：Myasthenia gravis(MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper(Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain ***, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha(AChRa) subunit(RAChR97–116)-induced experimental autoimmune myasthenia gravis(EAMG). This model presented mild bodyweight loss 10 days after the first immunization(representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization(representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In cocultures of Tfh cells and B cells, the number of IgG2 bsecreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4^+/Bcl-6^+ T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, wehypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.