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A tonsil organoid model reveals Epstein-Barr virus infected germinal center B cell states during primary infection

Mitul, M. T.; Sun, Y.; Yates, T. B.; Sureshchandra, S.; Kastenschmidt, J. M.; Sorn, A. M.; Wagoner, Z. W.; Joloya, E. M.; Nair, A. K.; Daugherty, A.; Saligrama, N.; Ahuja, G.; Zhong, Q.; Trask, D.; Kottyan, L. C.; Weirauch, M. T.; Forney, C.; Gewurz, B. E.; Wagar, L. E.

2026-01-15 immunology
10.64898/2026.01.15.699764 bioRxiv
Show abstract

Epstein-Barr virus (EBV) colonizes secondary lymphoid tissues to establish persistent infection and is strongly associated with malignancy and autoimmunity. Our understanding of EBV infection biology is hindered by a lack of models that capture infected B cell activity in the lymphoid tissue microenvironment. We therefore developed an EBV human tonsil organoid model to evaluate key B cell states and antiviral responses, including after primary infection. EBV promoted B cell differentiation into germinal center (GC)-like phenotypes and transcriptomic analyses highlighted numerous B cell transcriptional programs unique to EBV-infected cells. B cell receptor repertoire analysis revealed that most EBV-infected B cells underwent class switching but only rarely participated in somatic hypermutation. CD4 T cells, highly activated by organoid infection, limited EBV+ B cell outgrowth. Our findings demonstrate human tonsil organoids as a physiologically relevant model to investigate key aspects of EBV immunity and pathogenesis.

Published in Proceedings of the National Academy of Sciences (predicted rank #8) · training set

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