SARS-CoV-2 infection and vaccination elicit distinct pharyngeal mucosal B cell responses in children
Abstract Mucosal immunity is an important correlate of protection against respiratory infections such as SARS-CoV-2. Comparing B cell responses to vaccines and infection at relevant mucosal sites may provide unique and important insights into tissue immunity. Here, we characterize antigen-specific B cells in the tonsils, adenoids, and peripheral blood of children who had been infected with SARS-CoV-2 or vaccinated with SARS-CoV-2 mRNA vaccines. SARS-CoV-2-specific switched memory B cells (B SM ) are found in the pharyngeal lymphoid tissues and blood after vaccination or infection. However, infection generates a higher proportion of IgA + B SM and CXCR3 + CD21 + B SM . CXCR3 + CD21 + B SM show distinct spatial localization, greater clonal expansion and increased propensity for plasma cell differentiation compared to their CXCR3 - counterparts, accompanied by persistent activation of innate and T follicular helper cells in the tissues. Our data provide evidence for tissue-specific B cell memory after either SARS-CoV-2 vaccination or infection, but with distinct characteristics that can influence the quality, durability, and localization of immunity.
Authors
- Rachel Sparks (ORCID: https://orcid.org/0000-0001-8216-5084)
- Juanjie Tang (ORCID: https://orcid.org/0000-0002-5791-6082)
- Dominic P. Golec (ORCID: https://orcid.org/0000-0002-2741-3302)
- Andrew J. Martins (ORCID: https://orcid.org/0000-0002-1832-1924)
- Sara Pourhashemi
- Foo Cheung
- Kenneth B. Hoehn (ORCID: https://orcid.org/0000-0003-0411-4307)
- Lela Kardava
- Iyadh Douagi (ORCID: https://orcid.org/0000-0002-3221-8667)
- Clarisa M. Buckner (ORCID: https://orcid.org/0000-0002-8178-8076)
- Kalpana Manthiram (ORCID: https://orcid.org/0000-0001-6451-8173)
- Lorenza Bellusci (ORCID: https://orcid.org/0000-0001-9945-1706)
- Surender Khurana (ORCID: https://orcid.org/0000-0002-0593-7965)
- Gabrielle Grubbs (ORCID: https://orcid.org/0000-0003-4302-9535)
- Juraj Kabát (ORCID: https://orcid.org/0000-0001-8636-542X)
- Galina Koroleva
- Pamela Mudd
- Margery Smelkinson (ORCID: https://orcid.org/0000-0001-7777-5574)
- Justin Lack
- Tovah E. Markowitz
- Asya Khleborodova
- Lihong Shi (ORCID: https://orcid.org/0000-0002-6604-2065)
- Susan Moir (ORCID: https://orcid.org/0000-0002-0163-6911)
- Qin Xu (ORCID: https://orcid.org/0000-0003-1812-3108)
- Liya Wang
- Elizabeth Rice
- John S. Tsang (ORCID: https://orcid.org/0000-0003-3186-3047)
- Martha Kirby (ORCID: https://orcid.org/0000-0001-7157-7964)
- Craig Martens
- Can Liu (ORCID: https://orcid.org/0000-0002-8411-3891)
- Pamela L. Schwartzberg (ORCID: https://orcid.org/0000-0001-6318-9187)
- Richard Apps
- Hengameh Behzadpour (ORCID: https://orcid.org/0000-0002-0050-8336)
- Aparna Kotekar
Institutions
- Dartmouth College (US)
- National Institutes of Health (US)
- Center for Biologics Evaluation and Research (US)
- Children's National (US)
- George Washington University (US)
- Yale University (US)
- National Human Genome Research Institute (US)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-22
- DOI
- https://doi.org/10.1038/s41467-026-72996-3
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases