Exposure to the Epstein-Barr viral antigen induces affinity-maturated anti-myelin antibodies.

Abstract

Abstract Multiple Sclerosis (MS) is an autoimmune chronic inflammatory disease of central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered as one of the possible mechanisms of MS triggering. Previously we showed that monoclonal myelin basic protein (MBP)-specific IgGs are cross-reactive with Epstein-Barr virus (EBV) protein LMP-1. Here we report evidence that exposure of mice to LMP1 may result in induction of myelin-reactive autoantibodies in vivo. Only part of such anti-MBP antibodies are cross-reactive towards LMP1 but majority is occurred as a result of epitope spreading. We suggest that chronic contact with viral antigen rather than multiple rapid exposures to it is more sufficient in inducing switch of B cells from viral to myelin antigen. Moreover, even in inbred animals being almost identical in terms of genome, such switch was observed only in 20% of animals, indicating that this evidence is occurred by a chance rather than systematically. Our findings provide novel insights into still enigmatic link between EBV infection and MS development, determining several criteria that are beneficial for induction of self-reacting antibodies on the background of viral infection. Current study was supported by Russian Science Foundation grant #17-74-30019.