A tonsil organoid model reveals Epstein-Barr virus infected germinal center B cell states during primary infection
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 <sup>+</sup> B cell outgrowth. Our findings demonstrate human tonsil organoids as a physiologically relevant model to investigate key aspects of EBV immunity and pathogenesis.
Authors
- Gurpreet S. Ahuja (ORCID: https://orcid.org/0000-0002-3196-0819)
- Jenna M. Kastenschmidt (ORCID: https://orcid.org/0000-0002-0067-5142)
- E. Wagar Lisa
- Zachary W. Wagoner (ORCID: https://orcid.org/0000-0002-0354-5407)
- Andrew M. Sorn (ORCID: https://orcid.org/0000-0001-8660-1533)
- Erika Joloya (ORCID: https://orcid.org/0000-0002-4974-1657)
- Suhas Sureshchandra (ORCID: https://orcid.org/0000-0002-4141-8564)
- Mahina Tabassum Mitul (ORCID: https://orcid.org/0000-0002-5344-6810)
- Naresha Saligrama (ORCID: https://orcid.org/0000-0003-2526-7150)
- Allyssa L. Daugherty (ORCID: https://orcid.org/0000-0001-8428-0422)
- Benjamin E. Gewurz (ORCID: https://orcid.org/0000-0002-3965-3418)
- Douglas K. Trask (ORCID: https://orcid.org/0000-0003-0550-442X)
- Timothy B. Yates
- Yizhe Sun
- Carmy Forney (ORCID: https://orcid.org/0000-0001-6418-5794)
- Qui Zhong
- Leah C. Kottyan
- Arjun K. Nair
- Matthew T. Weirauch
Institutions
- Cincinnati Children's Hospital Medical Center (US)
- Children's Hospital of Orange County (US)
- University of California, Irvine (US)
- Washington University in St. Louis (US)
- Massachusetts General Hospital (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-01-15
- DOI
- https://doi.org/10.64898/2026.01.15.699764
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- National Center for Advancing Translational Sciences