Pathogenesis of MHV-induced demyelination

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DESCRIPTION (provided by applicant): C57B1/6 (B6) mice infected with mouse hepatitis virus, strain JHM (MHV) develop either an acute encephalitis or chronic demyelinating disease. This demyelinating disease is a model for the human disease multiple sclerosis. We are interested in the immunological mediators of demyelination in this model. In our model, a percentage of mice protected from the acute encephalitis by maternal antibody develop a demyelinating disease We have previously observed in this model of demyelination that roughly twenty percent of the lymphocytes infiltrating the CNS are B cells, although no serum antibody can be measured in these mice. Additionally, nude (athymic) mice develop a demyelinating disease in which some 70 percent of lymphocytes in the CNS are B cells. The function of these B cells has not been characterized. In order to investigate the role of these cells in demyelination, three specific aims will be pursued: 1) To characterize the nature of the B cell response in the MHV-infected CNS; 2) To investigate failure of antibody production in the chronic demyelinating disease; and 3) To determine the immunological effectors of MHV-JHM disease in nude mice.