B cell αv integrin regulates germinal center derived lung-resident IgA B cell responses following influenza virus infection

Abstract

AbstractEmerging studies have highlighted the importance of tissue-resident B cells in the lungs for protective immunity against respiratory viruses. However, mechanisms controlling maintenance of B cell responses at respiratory sites such as lungs remain obscure. We have previously shown that the αv family of integrins limit B cell responses to antigens containing Toll-like receptor ligands, therefore deletion of B cell αv integrins in mice, enhances long-lived B cell responses against viral antigens, after systemic immunization. Here, we investigated whether αv can also regulate B cell responses at the respiratory tract, during viral infection. Our data show that αv integrin restricts development of lung-resident B cells and loss of B cell αv promotes generation of lung-resident IgA B cell responses following influenza A virus (IAV) infection of mice. Analysis of infection induced B cells in the lungs showed that loss of B cell αv promotes persistence of germinal center (GC) reactions locally in the lungs, leading to increases in lung-resident IgA+ GC and memory B cells, cross-reactive to antigenic variants. Thus, these studies reveal how IgA B cells are maintained in the lungs and point to a new strategy to improve the durability of lung-resident B cell responses for IAV vaccine efficacy.