Departments of Neurology and Ophthalmology and Neuroscience Program (J.L.B.), University of Colorado, Denver; Department of Neurology (K.C.O.), Yale University School of Medicine, New Haven, CT; Neuroimmunology Unit (A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Department of Neurology (S.S.Z., H.-C.v.B.), UCSF School of Medicine, San Francisco, CA; Department of Neurology (B.H.), Technische Universität München, Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; Department of Immunology (T.F.T.), Duke University Medical Center, Durham, NC; Departments of Neurology and Neurotherapeutics (O.S.), University of Texas Southwestern Medical Center, Dallas, TX; Department of Medicine (M.R.Y.), Divisions of Molecular Medicine and Infectious Diseases, University of California, Los Angeles; Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; Departments of Ophthalmology and Visual Sciences and Internal Medicine (T.J.S.), University of Michigan Medical School, Ann Arbor; and Institute of Neuropathology (C.S.), University Medical Center, Göttingen, Germany.
Neurol Neuroimmunol Neuroinflamm. 2015 May 7;2(3):e104. doi: 10.1212/NXI.0000000000000104. eCollection 2015 Jun.
Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the CNS that predominantly affects the spinal cord and optic nerves. A majority (approximately 75%) of patients with NMO are seropositive for autoantibodies against the astrocyte water channel aquaporin-4 (AQP4). These autoantibodies are predominantly IgG1, and considerable evidence supports their pathogenicity, presumably by binding to AQP4 on CNS astrocytes, resulting in astrocyte injury and inflammation. Convergent clinical and laboratory-based investigations have indicated that B cells play a fundamental role in NMO immunopathology. Multiple mechanisms have been hypothesized: AQP4 autoantibody production, enhanced proinflammatory B cell and plasmablast activity, aberrant B cell tolerance checkpoints, diminished B cell regulatory function, and loss of B cell anergy. Accordingly, many current off-label therapies for NMO deplete B cells or modulate their activity. Understanding the role and mechanisms whereby B cells contribute to initiation, maintenance, and propagation of disease activity is important to advancing our understanding of NMO pathogenesis and developing effective disease-specific therapies.
视神经脊髓炎（NMO）是一种中枢神经系统的炎症性自身免疫性疾病，主要影响脊髓和视神经。大多数（约 75%）NMO 患者的血清中存在针对水通道蛋白 4（AQP4）的自身抗体。这些自身抗体主要为 IgG1，大量证据支持其致病性，可能通过与中枢神经系统星形胶质细胞上的 AQP4 结合，导致星形胶质细胞损伤和炎症。临床和基于实验室的综合研究表明，B 细胞在 NMO 免疫病理学中起着重要作用。已经提出了多种机制：AQP4 自身抗体的产生、增强的促炎 B 细胞和浆母细胞活性、异常的 B 细胞耐受检查点、B 细胞调节功能减弱以及 B 细胞失能。因此，许多目前用于 NMO 的非适应证治疗方法会耗尽 B 细胞或调节其活性。了解 B 细胞在疾病活动的启动、维持和传播中的作用和机制，对于深入了解 NMO 的发病机制和开发有效的疾病特异性治疗方法非常重要。
