B-cell-intrinsic MHCII signaling promotes microbiota diversity

Abstract

Abstract The expression of major histocompatibility complex class II (MHCII) molecules is essential for the formation of germinal centers (GC) in lymphoid follicles, which are the primary sites for the generation of T-cell-dependent (TD) high-affinity antibody responses. Gut peyer's patches (PPs) are the dominant peripheral lymphoid tissues that give rise to TD antibody (primarily immunoglobulin A (IgA)) responses generated against the gut microbiota. While it is anticipated, a requirement of B-cell-intrinsic MHCII expression for GC formation has never been formally described. Additionally, while anti-commensal TD IgA responses have been shown to regulate microbiota composition and function, to what degree B-cell-intrinsic MHCII influences this process is also undefined. Here, we use a RAG1−/− adoptive transfer model, where RAG1−/− mice are either reconstituted with naive CD4+ T cells and MHCII+ B cells or naive CD4+ T cells and MHCII−B cells to address these gaps in our knowledge. Results from these experiments demonstrate that B-cell-intrinsic MHCII signaling is a strict requirement for GC-TFH cell development. Consequently, B-cell-intrinsic MHCII signaling promotes the generation of high-affinity anti-commensal IgA responses in the gut, which lead to increased species richness within the fecal but not small intestinal microbial community. Collectively, our data suggest that B-cell-intrinsic MHCII signaling is crucial for the generation of high-affinity anti-commensal IgA responses generated against the gut microbiota, and that this response favors a more diverse bacterial community.