Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites

Resident memory B (BRM) cells develop and persist in the lungs of influenza-infected mice and humans; however, their contribution to recall responses has not been defined. Here, we used two-photon microscopy to visualize BRM cells within the lungs of influenza -virus immune and reinfected mice. Prior to re-exposure, BRM cells were sparsely scattered throughout the tissue, displaying limited motility. Within 24 h of rechallenge, these cells increased their migratory capacity, localized to infected sites, and subsequently differentiated into plasma cells. Alveolar macrophages mediated this process, in part by inducing expression of chemokines CXCL9 and CXCL10 from infiltrating inflammatory cells. This led to the recruitment of chemokine receptor CXCR3-expressing BRM cells to infected regions and increased local antibody concentrations. Our study uncovers spatiotemporal mechanisms that regulate lung BRM cell reactivation and demonstrates their capacity to rapidly deliver antibodies in a highly localized manner to sites of viral replication. [Display omitted] •Lung BRM cells localize to the alveoli and display confined probing behavior•Upon rechallenge, BRM cells increase their motility and accumulate in infected foci•BRM cell mobilization is followed by PC formation in sites of viral replication•Alveolar macrophages orchestrate this process via induction of IFNγ and CXCR3 ligands Resident memory B cells develop and persist in the lungs of influenza-infected hosts. Using 3D and live-imaging analysis of explant lung sections, MacLean et al. uncover cellular and molecular mechanisms that orchestrate the activation of these cells during secondary infection, leading to rapid delivery of antibodies in a highly localized manner directly to sites of viral replication.