Memory B cells are critical in gamma herpes virus driven disease enhancement of a mouse model for MS (BA2P.124)

Abstract

Abstract Genetic and environmental factors are known to be involved in the development of Multiple Sclerosis. However, the mechanism describing how these factors are responsible for the onset of MS has not been elucidated. One of the environmental factors believed to play an important role in the development of MS is previous infection with the Epstein Barr Virus (EBV). The study of the relationship between MS and EBV remains elusive since EBV only infects humans. We hypothesized that latent EBV infection alters the immune system’s response in genetically predisposed individuals, thereby exacerbating autoimmunity. To address this question our lab previously developed a model where latent infection with murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, enhances the symptoms of experimental autoimmune encephalomyelitis (EAE), which closely resembles MS pathogenesis. These enhanced symptoms are driven by the upregulation of CD40 on dendritic cells (DCs) of latently infected mice which drives the priming of a strong TH1 response and a decrease in Tregs frequencies. Latency of γHV-68 mainly occurs in memory B cells and the virus is not found in the DCs driving the TH1 response. Here we demonstrate that latently infected memory B cells are the cells responsible for the upregulation of CD40 in DCs, most likely through the upregulation of type I interferons in DCs. This represents a novel mechanism by which infection with EBV can influence MS and other autoimmune diseases.