Mast cells crosstalk with B cells in the gut and sustain IgA response in the inflamed intestine. Issue 2 (14th October 2020) - Valeri, Viviana
Abstract: B lymphocytes are among the cell types whose effector functions are modulated by mast cells (MCs). The B/MC crosstalk emerged in several pathological settings, notably the colon of inflammatory bowel disease (IBD) patients is a privileged site in which MCs and IgA + cells physically interact. Herein, by inducing conditional depletion of MCs in red MC and basophil (RMB) mice, we show that MCs control B cell distribution in the gut and IgA serum levels. Moreover, in dextran sulfate sodium (DSS)‐treated RMB mice, the presence of MCs is fundamental for the enlargement of the IgA + population in the bowel and the increase of systemic IgA production. Since both conventional B‐2 and peritoneal‐derived B cells populate the intestine and communicate with MCs in physiological conditions and during inflammation, we further explored this interplay through the use of co‐cultures. We show that MCs finely regulate different aspects of splenic B cell biology while peritoneal B cells are unresponsive to the supporting effects provided by MCs. Interestingly, peritoneal B cells induce a pro‐inflammatory skewing in MCs, characterized by increased ST2 and TNF‐α expression. Altogether, this study uncovers the versatility of the B/MC liaison and highlights key aspects for the resolution of intestinal inflammation. Abstract : This study provides evidences for the bi‐directional crosstalk between B lymphocytes and mast cells and, for the first time in vivo, describes a peculiar role of mast cells in regulating B‐cell biology in the intestine and the production of local and systemic IgA, both in homeostasis and during intestinal inflammation.