T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis.
The identification of myelin oligodendrocyte glycoprotein (MOG) as a target for autoantibody-mediated demyelination in experimental autoimmune encephalomyelitis (EAE) resulted in the re-evaluation of the role of B cell responses to myelin autoantigens in the immunopathogenesis of multiple sclerosis. MOG is a central nervous system specific myelin glycoprotein that is expressed preferentially on the outermost surface of the myelin sheath. Although MOG is only a minor component of CNS myelin it is highly immunogenic, inducing severe EAE in both rodents and primates. In rat and marmoset models of MOG-induced EAE demyelination is antibody-dependent and reproduces the immunopathology seen in many cases of MS. In contrast, in mice inflammation in the CNS can result in demyelination in the absence of a MOG-specific B cell response, although if present this will enhance disease severity and demyelination. Clinical studies indicate that autoimmune responses to MOG are enhanced in many CNS diseases and implicate MOG-specific B cell responses in the immunopathogenesis of multiple sclerosis. This review provides a summary of our current understanding of MOG as a target autoantigen in EAE and MS, and addresses the crucial question as to how immune tolerance to MOG may be maintained in the healthy individual.
Iglesias
A
A
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Bauer
J
J
Litzenburger
T
T
Schubart
A
A
Linington
C
C
D000820:Animal Diseases; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007167:Immunotherapy; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; C571326:MOG protein, human; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein