Critical role of antigen-specific antibody in experimental autoimmune encephalomyelitis induced by recombinant myelin oligodendrocyte glycoprotein.
The role of B cells and antibody in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) remains controversial. We previously demonstrated that B cells are required for EAE to be induced by the 120-amino acid extracellular domain of myelin oligodendrocyte glycoprotein (MOG). In the present study, the role of B cells in MOG-induced EAE was further characterized. Passive transfer of activated B cells or serum from MOG-primed wild-type (WT) mice was found to reconstitute the ability for clinical and histological EAE to be induced in MOG-immunized B cell-deficient mice. MOG-induced EAE did not occur with transfer of B cells that had been nonspecifically activated by lipopolysaccharide or isolated from naïve or myelin basic protein (MBP)-primed WT mice. Likewise, MOG-primed serum, but not naive serum or serum from MBP-, Hen egg lysozyme-, or MOG(35-55)-primed mice, led to EAE in B cell-/- animals. While both MOG-primed B cells and serum reconstituted the ability for disease induction, MOG-primed serum was much more efficient, leading to clinical and histological EAE similar to that seen in the WT. Injection of MOG serum into healthy B cell-/- mice 30 days after MOG immunization led to rapid appearance of clinical signs and CNS inflammation, indicating that an antigen-specific factor is necessary for initiation of CNS inflammation,and not just demyelination. These data strongly suggest that MOG-specific antibody is critical to the initiation of MOG-induced murine EAE.
Lyons
Jeri-Anne
JA
Department of Neurology and Neurosurgery, Washington University School of Medicine, Saint Louis, MO 63110, USA. lyonsj@neuro.wustl.edu
Ramsbottom
Michael J
MJ
Cross
Anne H
AH
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D006023:Glycoproteins / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000009:adverse effects; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D013116:Spinal Cord / Q000473:pathology
D001323:Autoantibodies; D001324:Autoantigens; D006023:Glycoproteins; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)