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

Xu, Qin; Shi, Lihong; Center for Human Immunology; Liu, Can; Kabat, Juraj; Behzadpour, Hengameh; Kardava, Lela; Markowitz, Tovah E et al. · Nat Commun · 2026

basic_science · Level V

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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<sub>SM</sub>) are found in the pharyngeal lymphoid tissues and blood after vaccination or infection. However, infection generates a higher proportion of IgA<sup>+</sup> B<sub>SM</sub> and CXCR3<sup>+</sup>CD21<sup>+</sup> B<sub>SM</sub>. CXCR3<sup>+</sup>CD21<sup>+</sup> B<sub>SM</sub> show distinct spatial localization, greater clonal expansion and increased propensity for plasma cell differentiation compared to their CXCR3<sup>-</sup> 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.