EBV induces CNS homing of B cells attracting inflammatory T cells

• 成果类型: Article
• 署名作者: Laderach, Fabienne; Piteros, Ioannis; Fennell, Eanna; Bremer, Elena; Last, Mette; Schmid, Sandra; Rieble, Lisa; Campbell, Caroline; Ludwig-Portugall, Isis; Bornemann, Lea; Gruhl, Alexander; Eulitz, Klaus; Gueguen, Paul; Mietz, Juliane; Mueller, Anne; Pezzino, Gaetana; Schmitz, Juergen; Ferlazzo, Guido; Mautner, Josef; Munz, Christian
• 署名单位: University of Zurich; University of Limerick; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Swiss Federal Institutes of Technology Domain; University of Zurich; ETH Zurich; University of Zurich; University of Genoa
• 刊物名称: NATURE
• ISSN/ISSBN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-025-09378-0
• 发表日期: 2025-10-02
• 关键词: epstein-barr-virus; multiple-sclerosis; rituximab; antibody

摘要

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+ 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.