Influenza-specific lung-resident memory B cells assist CD4 recall responses during challenge infections 2971

Abstract Description During secondary influenza A virus (IAV) infections, lung-resident memory B cells (BRMs) enhance early responses, even when their secreted antibodies do not neutralize the virus’s surface glycoproteins. However, it is unclear whether lung BRMs influence recall responses through antibody-independent mechanisms. Here, we show that agammaglobulinemic AID−/−μs−/− mice, which lack antibodies, maintained normal CD4 and CD8 T cell numbers after heterotypic challenge. In contrast, B cell-deficient μMT mice that received immune serum during the primary infection showed reduced CD4 but not CD8 recall responses compared to B cell-sufficient C57BL/6 mice. Additionally, memory μMT mice boosted with immune serum before rechallenge with purified IAV nucleoprotein showed decreased T cell recall responses. Using B cell-specific MHCII conditional knockout mice, we found that MHCII deletion after memory establishment impaired lung germinal center B cell populations and significantly reduced the number of flu-specific CD4 T cells following a heterotypic challenge. This indicates that local B-T interactions persist after memory establishment and are important for memory cell reactivation. Lastly, in IAV-PR8-OVA memory mice challenged with DQ-OVA, lung memory B cells effectively captured and processed antigens on MHCII molecules. Taken together, these results indicate that lung BRMs support CD4 recall responses, especially at low antigen doses, by facilitating antigen uptake and presentation. Funding Sources NIH 1R01AI153413-01 Protective functions of influenza-specific lung-resident memory B cells Topic Categories Mucosal and Regional Immunology (MUC)