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Läderach, F.* ; Piteros, I.* ; Fennell, E.* ; Bremer, E.* ; Last, M. ; Schmid, S.* ; Rieble, L.* ; Campbell, C.D.* ; Ludwig-Portugall, I.* ; Bornemann, L.* ; Gruhl, A.* ; Eulitz, K.* ; Gueguen, P.* ; Mietz, J.* ; Müller, A.* ; Pezzino, G.* ; Schmitz, J.* ; Ferlazzo, G.* ; Mautner, J. ; Münz, C.*

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

Nature 646, 171-179 (2025)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Epstein-barr-virus; Multiple-sclerosis; Rituximab; Antibody
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 646, Heft: 8083, Seiten: 171-179 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen University of Zurich (Forschungskredit)
Cancer Research Switzerland
Swiss MS Society
Swiss State Secretariat for Education, Research and Innovation for EU
Sobek Foundation
Swiss Vaccine Research Institute
Vontobel Foundation
Roche
Swiss National Science Foundation