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

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.