Enhancement of T Follicular Helper Cell-Mediated Humoral Immunity Reponses During Development of Experimental Autoimmune Myasthenia Gravis
Autor: | Siying Qu, Ying-Zhe Cui, Bo Sun, Tongshuai Zhang, Guangyou Wang, Jiarui Zhao, Qingfei Kong, Lili Mu, Hulun Li, Lulu Chang |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Physiology 03 medical and health sciences 0302 clinical medicine Immune system Animals Medicine Receptors Cholinergic Lymph node Autoimmune disease B-Lymphocytes biology business.industry General Neuroscience Germinal center Receptor Cross-Talk T-Lymphocytes Helper-Inducer General Medicine medicine.disease Myasthenia gravis Immunity Humoral Myasthenia Gravis Autoimmune Experimental Disease Models Animal Protein Subunits 030104 developmental biology medicine.anatomical_structure Immunization Rats Inbred Lew Humoral immunity Immunology Proto-Oncogene Proteins c-bcl-6 biology.protein Female Original Article Lymph Nodes Antibody business 030217 neurology & neurosurgery |
Zdroj: | Neurosci Bull |
ISSN: | 1995-8218 1673-7067 |
Popis: | 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 (AChRα) subunit (R-AChR(97–116))-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight 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 co-cultures of Tfh cells and B cells, the number of IgG2b-secreting 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, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG. |
Databáze: | OpenAIRE |
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