title: B lymphocytes in neuromyelitis optica.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bennett
authors.affiliation: 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.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.affiliation: 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.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: 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.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.affiliation: 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.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
authors.affiliation: 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.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.affiliation: 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.
authors.forename: H-Christian
authors.initials: HC
authors.lastname: von Büdingen
authors.affiliation: 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.
authors.forename: Olaf
authors.initials: O
authors.lastname: Stuve
authors.affiliation: 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.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.affiliation: 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.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann