EBV induces CNS homing of B cells attracting inflammatory T cells.

Abstract

Epidemiological data have identified Epstein-Barr virus (EBV) infection as the main environmental risk factor for multiple sclerosis, the predominant autoimmune disease of the central nervous system (CNS)¹. However, how EBV infection initiates multiple sclerosis pathogenesis remains unclear. Here we demonstrate that EBV expands oligoclonal T-bet⁺CXCR3⁺ B cells that home to the CNS in humanized mice. Effector memory CD8⁺ T cells and CD4⁺ T_H1 cells as well as CD4⁺ T_H17 cells co-migrate to the brain of EBV-infected humanized mice. T-bet⁺CXCR3⁺ B cells can colonize submeningeal brain regions in the absence of other lymphocytes and attract T cells. Depletion of B cells with rituximab or blocking of CXCR3 significantly decreases lymphocyte infiltration into the CNS. Thus, we suggest that symptomatic primary EBV infection generates B cell subsets that gain access to the CNS, attract T cells and thereby initiate multiple sclerosis.