Mast Cells Control the Expansion and Differentiation of IL-10–Competent B Cells

Abstract

The discovery of B cell subsets with regulatory properties, dependent on IL-10 production, has expanded our view on the mechanisms that control inflammation. Regulatory B cells acquire the ability to produce IL-10 in a stepwise process: first, they become IL-10 competent, a poised state in which B cells are sensitive to trigger signals but do not actually express the Il-10 gene; then, when exposed to appropriate stimuli, they start producing IL-10. Even if the existence of IL-10–competent B cells is now well established, it is not yet known how different immune cell types cross talk with B cells and affect IL-10–competent B cell differentiation and expansion. Mast cells (MCs) contribute to the differentiation and influence the effector functions of various immune cells, including B lymphocytes. In this study, we explored whether MCs could play a role in the expansion of IL-10–competent B cells and addressed the in vivo relevance of MC deficiency on the generation of these cells. We show that MCs can expand IL-10–competent B cells, but they do not directly induce IL-10 production; moreover, the absence of MCs negatively affects IL-10–competent B cell differentiation. Noteworthy, our findings reveal that the CD40L/CD40 axis plays a significant role in MC-driven expansion of IL-10–competent B cells in vitro and highlight the importance of MC CD40L signaling in the colon.