EBV enables B cells to bypass death in the CNS, linking viral infection to autoimmune demyelination in multiple sclerosis. The importance of B cells in the pathogenesis of multiple sclerosis (MS) has been firmly established by the notable clinical efficacy of anti-CD20 antibody therapies. In a recent study, Kim et al. addressed these questions using mouse models, intravital two-photon microscopy, and single-cell analyses. They visualized naive myelin-reactive B cells that infiltrate the central nervous system (CNS) after viral infection and directly acquire myelin antigens from the brain parenchyma. Under normal circumstances, such an antigen encounter in the absence of T cell help (CD40L) leads to rapid cell death. Crucially, the authors identified the EBV latent gene LMP1 as a decisive factor in overriding this checkpoint. By mimicking CD40 signaling, LMP1 allowed B cells to bypass immunological checkpoints and drive demyelination independently of T cell help.
