B Cell Expansion Hinders the Stroma-Epithelium Regenerative Crosstalk During Mucosal Healing

Little is known about the pro-resolution role of immune cells recruited to damaged tissue. Using an experimental model of intestinal epithelial damage and repair, we identified B cells as the dominant cell type in the healing colon. Single-cell RNA-sequencing (scRNAseq) revealed the expansion of an IFN-induced B cell subset during experimental mucosal healing which was associated with colitis severity. In line with this, B cell depletion during mucosal healing resulted in accelerated recovery upon injury, which was associated with enhanced expression of tissue remodeling genes. scRNA-seq from the epithelial and stromal compartment confirmed that lack of B cells during mucosal healing alters gene activity programs associated with tissue remodeling. Combined scRNAseq and spatial transcriptomic analysis showed that IFN-induced B cells are located at sites of damage/remodeling and that absence of B cells resulted in decreased potential interaction and co-localization between stromal and epithelial cells. Thus, we identified a previously undescribed role of B cells impairing cell-cell interactions during mucosal healing.