Lung B cells promote early pathogen dissemination and hasten death from inhalation anthrax

Abstract

Sampling of mucosal antigens regulates immune responses but may also promote dissemination of mucosal pathogens. Lung dendritic cells (LDCs) capture antigens and traffic them to lung-draining lymph nodes (LDLNs) dependent on the chemokine receptor CCR7 (chemokine (C-C motif) receptor 7). LDCs also capture lung pathogens such as Bacillus anthracis (BA). However, we show here that the initial traffic of BA spores from lungs to LDLNs is largely independent of LDCs and CCR7, occurring instead in association with B cells. BA spores rapidly bound B cells in lungs and cultured mouse and human B cells. Binding was independent of the B-cell receptor (BCR). B cells instilled in the lungs trafficked to LDLNs and BA spore traffic to LDLNs was impaired by B-cell deficiency. Depletion of B cells also delayed death of mice receiving a lethal BA infection. These results suggest that mucosal B cells traffic BA, and possibly other antigens, from lungs to LDLNs.