B-cell-intrinsic MHCII signaling limits bacteremia and systemic invasion by Citrobacter rodentium

Abstract

Abstract B-cell-intrinsic major histocompatibility complex class II (MHCII) antigen presentation is central to the development of T-cell-dependent antibody responses. However, the physiological significance of B-cell-intrinsic MHCII signaling during homeostatic conditions and infection are unknown. Here, using a B-cell-intrinsic MHCII knockout mouse model, we demonstrate that B-cell-intrinsic MHCII signaling is important for the development of systemic IgG1 and mucosal, high-affinity IgA responses. We also show that the conditional ablation of MHCII signaling on B cells results in a change in the microbiota composition, exhibiting a significant increase in the mucin-degrading bacteria Akkermansia muciniphila. This change in the microbiome is also associated with elevated bacterial dissemination from the gut into the systemic compartment under homeostatic conditions. Additionally, using a Citrobacter rodentium model of acute gastrointestinal infection, we also demonstrate the relevance of B-cell-intrinsic MHCII signaling in limiting invasion of the systemic compartment by an opportunistic enteric pathogen. Results from these experiments demonstrate that B-cell-intrinsic MHCII signaling is an important factor minimizing the physiological cost of microbial colonization of the gut. Supported by NIH R21AI142409, R01AI155887