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

Abstract

Lung-resident B cells are increasingly recognized as key contributors to protective immunity against respiratory viruses, yet the mechanisms that govern their generation and specialization remain poorly understood. Here, we identify B cell-intrinsic v integrin as a critical negative regulator of germinal center (GC) dynamics and memory B cell formation in the lung following influenza A virus (IAV) infection. Using B cell-specific v knockout mice, we show that loss of B cell v integrin leads to persistent GC activity within the inducible bronchus-associated lymphoid tissue and expansion of lung-resident memory B cells, including IgA+ and cross-reactive B cells capable of recognizing heterologous influenza variants. Single-cell transcriptomic and B cell receptor (BCR) sequence analyses reveal that v restricts clonal expansion and antigenic diversification of GC and memory B cells in the lung, but not in draining lymph nodes, indicating a spatially restricted mechanism of mucosal B cell regulation. These findings position v integrin as a key checkpoint that constrains local mucosal B cell evolution and suggest new strategies to improve mucosal vaccine efficacy by enhancing GC activity directly in the lung.