Nature Communications

SARS-CoV-2 infection and vaccination elicit distinct pharyngeal mucosal B cell responses in children

2026-05-22

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.

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DOI https://doi.org/10.1038/s41467-026-72996-3