B cells and the intestinal microbiome in time, space and place

The gut immune system is shaped by the continuous interaction with the microbiota. Here we dissect temporal, spatial and contextual layers of gut B cell responses. The microbiota impacts on the selection of the developing pool of pre-immune B cells that serves as substrate for B cell activation, expansion and differentiation. However, various aspects of the gut B cell response display unique features. In particular, occurrence of somatically mutated B cells, chronic gut germinal centers in T cell-deficient settings and polyreactive binding of gut IgA to the microbiota questioned the nature and microbiota-specificity of gut germinal centers. We propose a model to reconcile these observations incorporating recent work demonstrating microbiota-specificity of gut germinal centers. We speculate that adjuvant effects of the microbiota might modify permissiveness for B cell to enter and exit gut germinal centers. We propose that separating aspects of time, space and place facilitate the occasionally puzzling discussion of gut B cell responses to the microbiota.