title: B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis.
abstract: B cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis, in part as a result of the success of B cell-depletion therapy. Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the CNS have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis. Although B cell Ag presentation was suggested to regulate CNS inflammation during EAE, direct evidence that B cells can independently support Ag-specific autoimmune responses by CD4 T cells in EAE is lacking. Using a newly developed murine model of in vivo conditional expression of MHC class II, we reported previously that encephalitogenic CD4 T cells are incapable of inducing EAE when B cells are the sole APC. In this study, we find that B cells cooperate with dendritic cells to enhance EAE severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Further, increasing the precursor frequency of MOG-specific B cells, but not the addition of soluble MOG-specific Ab, is sufficient to drive EAE in mice expressing MHCII by B cells alone. These data support a model in which expansion of Ag-specific B cells during CNS autoimmunity amplifies cognate interactions between B and CD4 T cells and have the capacity to independently drive neuroinflammation at later stages of disease.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Chelsea R
authors.initials: CR
authors.lastname: Parker Harp
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Angela S
authors.initials: AS
authors.lastname: Archambault
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Julia
authors.initials: J
authors.lastname: Sim
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Ferris
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mikesell
authors.affiliation: Cancer Immunology, Inflammation, and Tolerance Program, Cancer Center and Department of Medicine, Georgia Regents University, Augusta, GA 30912;
authors.forename: Pandelakis A
authors.initials: PA
authors.lastname: Koni
authors.affiliation: Department of Dermatology, University of California at Davis School of Medicine, Sacramento, CA 95817; and.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Immunology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Linington
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: John H
authors.initials: JH
authors.lastname: Russell
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; wug@neuro.wustl.edu.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Wu
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage / Q000276:immunology*; D020078:Neurogenic Inflammation / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D063308:Myelin-Oligodendrocyte Glycoprotein