Increased Severity of Experimental Allergic Encephalomyelitis in lyn −/− Mice in the Absence of Elevated Proinflammatory Cytokine Response in the Central Nervous System

Abstract

lyn, a member of the src kinase family, is an important signaling molecule in B cells. lyn−/− mice display hyperactive B-1 cells and IgM hyperglobulinemia. The role of lyn on T cell function and development of Th1-mediated inflammatory disease is not known. Therefore, we examined the effect of disruption of the lyn gene on the development of experimental allergic encephalomyelitis (EAE), a well-established Th1-mediated autoimmune disease. Following immunization with myelin oligodendrocyte protein (MOG) p35-55, lyn−/− mice had higher clinical and pathological severity scores of EAE when compared with wild type (WT). The increase in the severity of EAE in lyn−/− mice was not associated with a commensurate increase in the production of proinflammatory cytokines in the CNS. lyn−/− mice with EAE showed elevation in serum anti-IgM MOG Ab levels over that seen in WT mice, along with a modest increase in the mRNA levels of complement C5 and its receptor, C5aR, in the spinal cord. Transfer of serum from MOG-immunized lyn−/− mice worsened EAE in WT mice, suggesting a pathogenic role for anti-MOG IgM Abs in EAE. These observations underscore the potential role of lyn in regulation of Th1-mediated disease and the role of autoantibodies and complement in the development of EAE.