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 ma...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 unclear.Here, 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.展开更多
基金supported by the National Natural Science Foundation of China(81000536,81471227,31371079,31671112 and 81430035)the China Postdoctoral Science Foundation(20100471094)+3 种基金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)
文摘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 unclear.Here, 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.
