Abstract
Multiple sclerosis (MS) is caused by a combination of genetic and environmental factors. It is believed that previous infection with Epstein Barr Virus (EBV) plays an important role in the development of MS. Previously, we developed a murine model where latent infection with gamma herpesvirus 68 (γHV-68), a murine homolog to EBV, enhanced the symptoms of experimental autoimmune encephalomyelitis (EAE), resulting in disease that more closely resembles MS in humans. Here, we explored the conditions that were necessary for EAE enhancement. We showed that latently infected CD19+IgD- B cells were capable of enhancing EAE symptoms when transferred from mice previously infected with γHV-68 into uninfected mice. We also observed a prevention of enhancement when B cells were depleted before infection. However, depletion after the establishment of latency only partially reduced EAE. This indicated the existence of a mechanism where B cells play an important role as antigen presenting cells (APCs) prior to EAE induction for the priming of Th1 cells. It is possible that these signals persist even after B cell depletion, strongly suggesting a paracrine signaling modulation of non-B cell APCs. These results strongly support the concept that EBV contributes to the development of autoimmunity and highlights the need for a vaccine against EBV that could limit or prevent multiple sclerosis development.