Targeting B cells for inflammatory bowel disease treatment: back to the future

B cells are critical to immune homeostasis at mucosal surfaces including those of the gastrointestinal tract. B cell-related abnormalities, comprising of a lympho-plasmacytic infiltrate, as well as anti-microbial antibodies, are well reported in patients with inflammatory bowel disease (IBD). However, B cell-targeting is not part of the therapeutic armamentarium in IBD. Recently, driven by the identification of genetic associations between IgG Fc receptors and IBD susceptibility, there has been renewed interest in defining the immunobiology of B cells during mucosal inflammation. Functional studies have demonstrated mechanisms of IgG-mediated disease pathogenesis and deep mucosal immunophenotyping using single cell RNA sequencing has elaborated a significant remodelling of the B cell compartment in IBD. In light of these novel data, here we discuss potential strategies to target B cell immunity in IBD. Finally, we discuss potential risks and pitfalls of these approaches and emphasize on distinguishing between homeostatic and pathological B cell signatures, allowing for a data-based, prudent therapeutic approach.