title: IFN-β treatment requires B cells for efficacy in neuroautoimmunity.
abstract: IFN-β remains the most widely prescribed treatment for relapsing remitting multiple sclerosis. Despite widespread use of IFN-β, the therapeutic mechanism is still partially understood. Particularly, the clinical relevance of increased B cell activity during IFN-β treatment is unclear. In this article, we show that IFN-β pushes some B cells into a transitional, regulatory population that is a critical mechanism for therapy. IFN-β treatment increases the absolute number of regulatory CD19(+)CD24(++)CD38(++) transitional B cells in peripheral blood relative to treatment-naive and Copaxone-treated patients. In addition, we found that transitional B cells from both healthy controls and IFN-β-treated MS patients are potent producers of IL-10, and that the capability of IFN-β to induce IL-10 is amplified when B cells are stimulated. Similar changes are seen in mice with experimental autoimmune encephalomyelitis. IFN-β treatment increases transitional and regulatory B cell populations, as well as IL-10 secretion in the spleen. Furthermore, we found that IFN-β increases autoantibody production, implicating humoral immune activation in B cell regulatory responses. Finally, we demonstrate that IFN-β therapy requires immune-regulatory B cells by showing that B cell-deficient mice do not benefit clinically or histopathologically from IFN-β treatment. These results have significant implications for the diagnosis and treatment of relapsing remitting multiple sclerosis.
authors: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305; Department of Neurology, University of California San Francisco, San Francisco, CA 94158; and.
authors: Ryan D
authors: RD
authors: Schubert
authors: Department of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
authors: Yang
authors: Y
authors: Hu
authors: Department of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
authors: Gaurav
authors: G
authors: Kumar
authors: Department of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
authors: Spencer
authors: S
authors: Szeto
authors: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305;
authors: Peter
authors: P
authors: Abraham
authors: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305;
authors: Johannes
authors: J
authors: Winderl
authors: Department of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
authors: Joel M
authors: JM
authors: Guthridge
authors: Department of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
authors: Gabriel
authors: G
authors: Pardo
authors: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305;
authors: Jeffrey
authors: J
authors: Dunn
authors: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305;
authors: Lawrence
authors: L
authors: Steinman
authors: Department of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104 bob-axtell@omrf.org.
authors: Robert C
authors: RC
authors: Axtell
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity / Q000187:drug effects*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D015398:Signal Transduction; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; C508609:IL10 protein, human; D007166:Immunosuppressive Agents; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10; D000068717:Glatiramer Acetate; D016899:Interferon-beta
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