title: C3d binding to the myelin oligodendrocyte glycoprotein results in an exacerbated experimental autoimmune encephalomyelitis.
abstract: The complement system is known to contribute to demyelination in multiple sclerosis and experimental autoimmune encephalomyelitis. However, there are few data concerning the natural adjuvant effect of C3d on the humoral response when it binds to myelin Ags. This study addresses the effect of C3d binding to the myelin oligodendrocyte glycoprotein (MOG) in the induction of experimental autoimmune encephalomyelitis in C57BL/6J mice. Immunization with human MOG coupled to C3d was found to accelerate the appearance of clinical signs of the disease and to enhance its severity compared with MOG-immunized mice. This finding was correlated with an increased infiltration of leukocytes into the central nervous system accompanied by increased complement activation and associated with areas of demyelination and axonal loss. Furthermore, B cell participation in the pathogenesis of the disease was determined by their increased capacity to act as APCs and to form germinal centers. Consistent with this, the production of MOG-specific Abs was found to be enhanced following MOG/C3d immunization. These results suggest that binding of C3d to self-Ags could increase the severity of an autoimmune disease by enhancing the adaptive autoimmune response.
authors.affiliation: INSERM U413, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides 23, University of Rouen, Place Emile Blondel, Mont Saint-Aignan Cedex, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jégou
authors.forename: Philippe
authors.initials: P
authors.lastname: Chan
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Schouft
authors.forename: Mark R
authors.initials: MR
authors.lastname: Griffiths
authors.forename: James W
authors.initials: JW
authors.lastname: Neal
authors.forename: Philippe
authors.initials: P
authors.lastname: Gasque
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Marc
authors.initials: M
authors.lastname: Fontaine
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D015933:Complement C3d / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D012720:Severity of Illness Index
chemical_list: C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D015933:Complement C3d