A tonsil organoid model reveals Epstein–Barr virus–infected germinal center B cell states during primary infection
- Mahina Tabassum Mitul
- Yizhe Sun
- Timothy B. Yates
- Suhas Sureshchandra
- Jenna M. Kastenschmidt
- Andrew M. Sorn
- Zachary W. Wagoner
- Erika M. Joloya
- Arjun K. Nair
- Allyssa Daugherty
- Naresha Saligrama
- Gurpreet Ahuja
- Qiu Zhong
- Douglas Trask
- Carmy Forney
- Rui Guo
- Matthew T. Weirauch
- Leah C. Kottyan
- Benjamin E. Gewurz
- Lisa E. Wagar
2026-08-13
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-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 + 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 in both primary and secondary EBV infection. Our findings demonstrate human tonsil organoids as a physiologically relevant model to investigate key aspects of EBV immunity and pathogenesis.