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)<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Bjornevik, K. et al. Longitudinal analysis reveals high prevalence of Epstein–Barr virus associated with multiple sclerosis. Science 375, 296–301 (2022)." href="https://www.nature.com/articles/s41586-025-09378-0#ref-CR1">1</a>. 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+ TH1 cells as well as CD4+ TH17 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.
EBV induces CNS homing of B cells attracting inflammatory T cells - Nature
Epstein–Barr virus infection generates a neuroinvasive B cell subset, which recruits activated T cells to the central nervous system, promoting multiple sclerosis.
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