The ion channel TRPM7 is required for B cell lymphopoiesis

Abstract The ion channel, transient receptor potential subfamily melastatin, member 7 (TRPM7) was first identified as critical for cell viability in the B cell line, DT40, by regulating cellular Mg2+ homeostasis. However, specific deletion of TRPM7 in T cells results in only a minor defect in thymocyte development and nearly normal numbers of peripheral T cells, raising the question of whether TRPM7 is in fact important for B cell development in vivo. Here, we generated a murine model in which TRPM7 is specifically deleted in B cells under control of the Mb1 promotor. We show that Mb1-Cre mediated deletion of TRPM7 results in a complete loss of peripheral B cells and a developmental block at the pro B cell stage in the bone marrow, coincident with the expression of Mb1. Importantly, we demonstrate using the in vitro OP9 stromal cell system of lymphopoiesis that supplementation with high levels of extracellular Mg2+ can partially support B cell development in TRPM7-deficient mice. Thus, our findings identify a critical role for TRPM7 in B cell lymphopoiesis.