title: B cells promote induction of experimental autoimmune encephalomyelitis by facilitating reactivation of T cells in the central nervous system.
abstract: The efficacy of rituximab treatment in multiple sclerosis has renewed interest in the role of B cells in CNS autoimmunity. In this study, we show that B cells are the predominant MHC class II(+) subset in the naive CNS in mice, and they constitutively express proinflammatory cytokines. Incidence of experimental autoimmune encephalomyelitis induced by adoptive transfer was significantly reduced in C3HeB/Fej μMT (B cell-deficient) mice, suggesting an important role for CNS B cells in initiating inflammatory responses. Initial T cell infiltration of the CNS occurred normally in μMT mice; however, lack of production of T cell cytokines and other immune mediators indicated impaired T cell reactivation. Subsequent recruitment of immune cells from the periphery driven by this initial T cell reactivation did not occur in μMT mice. B cells required exogenous IL-1β to reactivate Th17 but not Th1 cells in vitro. Similarly, reactivation of Th1 cells infiltrating the CNS was selectively impaired compared with Th17 cells in μMT mice, causing an increased Th17/Th1 ratio in the CNS at experimental autoimmune encephalomyelitis onset and enhanced brain inflammation. These studies reveal an important role for B cells within the CNS in reactivating T cells and influencing the clinical manifestation of disease.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98109.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Pierson
authors.forename: Ingunn M
authors.initials: IM
authors.lastname: Stromnes
authors.forename: Joan M
authors.initials: JM
authors.lastname: Goverman
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C587263:MOG protein, rat (79-90); C587264:MOG protein, rat (97-114); D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments