title: Intrathymic Tfh/B Cells Interaction Leads to Ectopic GCs Formation and Anti-AChR Antibody Production: Central Role in Triggering MG Occurrence.
abstract: Myasthenia gravis is a typical acetylcholine receptor (AChR) antibody-mediated autoimmune disease in which thymus frequently presents follicular hyperplasia or thymoma. It is now widely accepted that the thymus is probably the site of AChR autosensitization and autoantibody production. However, the exact mechanism that triggers intrathymic AChR antibody production is still unknown. T follicular helper cells, recently identified responsible for B cell maturation and antibody production in the secondary lymphoid organs, were involved in many autoimmune diseases. Newly studies found T follicular helper (Tfh) cells increased in the peripheral blood of myasthenia gravis (MG). Whether it appears in the thymus of MG and its role in the intrathymic B cells help and autoantibody production is unclear. Therefore, this study aims to determine in more detail whether Tfh/B cell interaction exist in MG thymus and to address its role in the ectopic germinal centers (GCs) formation and AChR antibody production. We observed the frequency of Tfh cells and its associated transcription factor Bcl-6, key cytokine IL-21 enhanced both in the thymocytes and peripheral blood mononuclear cells (PBMCs) of MG patients. In parallel, we also showed increased B cells and autoantibody titers in MG peripheral blood and thymus. Confocal microscope results demonstrated Tfh and B cells co-localized within the ectopic GCs in MG thymus, suggesting putative existence of Tfh/B cells interaction. In vitro studies further showed dynamic behavior of Tfh/B cells interaction and Tfh cells induced autoantibody secretion might through its effector cytokine IL-21. Altogether, our data demonstrated that intrathymic Tfh/B cells interaction played a key role in thymic ectopic GCs formation and anti-AChR antibody production, which might trigger MG occurrence.
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China.|Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.|Department of Neurology, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou, 730050, Gansu Province, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China.|Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chang
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China. lizhuyi@fmmu.edu.cn.
authors.forename: Zhuyi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China. yangkunkun@fmmu.edu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D011950:Receptors, Cholinergic
keywords: Anti-acetylcholine receptor antibody; Follicular helper T cells; Germinal centers; Myasthenia gravis; Thymus