title: B cell recognition of myelin oligodendrocyte glycoprotein autoantigen depends on immunization with protein rather than short peptide, while B cell invasion of the CNS in autoimmunity does not.
abstract: We develop a new fusion protein reagent (MOGtag), based on the extracellular domain of mouse myelin oligodendrocyte glycoprotein (MOG1-125), designed to induce autoimmune responses in mice that incorporates both T and B cell recognition of antigen. Reports of similar reagents, primarily based on foreign MOG proteins, rely largely on disease incidence and severity, with little analysis of the underlying immune response or pathology. We characterize the immune response and central nervous system autoimmune disease elicited by MOGtag in mice and find that it results in the formation of a T cell-dependent germinal center B cell response. Unlike immunization with the short MOG35-55 peptide, this response incorporated B cells able to recognize MOG protein. The autoimmune disease resulting from immunization with MOGtag was chronic with clear evidence of an ongoing immune response and active white and gray matter infiltration by T cells as well as formation of B cell clusters in the meninges. Interestingly, development of B cell clusters was not absolutely dependent on the ability of B cells to recognize MOG protein, as they were also present in mice immunized with short peptide and in mice with a mutant B cell receptor specific for an irrelevant antigen.
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Dang
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Rajiv W
authors.initials: RW
authors.lastname: Jain
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Craig
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address: skerfoot@uwo.ca.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kerfoot
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology* / Q000633:toxicity; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D001324:Autoantigens; D018992:Myelin-Associated Glycoprotein; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D049452:Green Fluorescent Proteins
keywords: B cells; EAE; Germinal center; MOG; T cells