Enhanced interferon-stimulated gene signatures in B cells following influenza B virus infection compared to influenza vaccination

These interferon-stimulated genes were not observed in B cells following influenza vaccination encompassing both IAV and IBV components or IAV infection in our patients. For HA-specific B cells, transcriptomic analysis revealed phenotypic differentiation and isotype class-switching following vaccination, with evidence of clonal sharing between memory and atypical B cell phenotypes. In in vitro influenza virus infection experiments, IBVs showed higher infectivity of human peripheral blood mononuclear cells, including B cells, in comparison to IAVs.

Additional co-culture of infected PBMCs with plasma obtained from patients hospitalized with IAV, IBV, COVID-19 and RSV increased the infectivity of immune cells by both IBV and IAV, suggesting that B cell infectivity we observed might also be driven by plasma mediators. IBV infection also resulted in reduced B cell proliferation compared to IAV, potentially associated with the antiproliferative effect of IFITM1. Our findings comparing and contrasting influenza-specific B cell responses elicited following acute influenza virus infection versus vaccination provide key insights into understanding B cell immunity towards IBV versus IAV infections, in contrast to vaccination responses, to inform rational vaccine design and therapeutic targets.