Selective Unresponsiveness to Conformational B Cell Epitopes of the Myelin Oligodendrocyte Glycoprotein in H-2^b Mice

Autoantibodies directed against conformation-dependent epitopes of the extracellular domain of the myelin oligodendrocyte glycoprotein (MOG(Igd)) play a major role in the immunopathogenesis of demyelination in experimental autoimmune encephalomyelitis. We now demonstrate that one or more genes encoded within the MHC selectively censor the ability of H-2(b) mice to mount this conformation-dependent autoantibody response, while leaving T and B cell responses to linear MOG(Igd) epitopes intact. This novel form of selective B cell unresponsiveness discriminates between pathogenic and nonpathogenic Ab responses to MOG and determines whether or not Ab-dependent effector mechanisms play an important role in the pathogenesis of MOG-induced experimental autoimmune encephalomyelitis in the mouse.