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The ion channel TRPM7 is required for B cell lymphopoiesis

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Sci. Signal.  05 Jun 2018:
Vol. 11, Issue 533, eaan2693
DOI: 10.1126/scisignal.aan2693

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B cell development demands ion flux

In various immune cell types, the divalent cation channel-kinase TRPM7 regulates cell survival, migration, and effector functions. Krishnamoorthy et al. found that B cell–specific deletion of TRPM7 blocked the development of mature peripheral B cells in mice. Loss of TRPM7, but not its kinase activity, increased the apoptosis of B cell precursors in the bone marrow. Supplementation with extracellular magnesium rescued the development of TRPM7-deficient B cells in vitro. These data suggest that the ion channel activity of TRPM7 is required for B cell development.

Abstract

The transient receptor potential (TRP) family is a large family of widely expressed ion channels that regulate the intracellular concentration of ions and metals and respond to various chemical and physical stimuli. TRP subfamily M member 7 (TRPM7) is unusual in that it contains both an ion channel and a kinase domain. TRPM7 is a divalent cation channel with preference for Ca2+ and Mg2+. It is required for the survival of DT40 cells, a B cell line; however, deletion of TRPM7 in T cells does not impair their development. We found that expression of TRPM7 was required for B cell development in mice. Mice that lacked TRPM7 in B cells failed to generate peripheral B cells because of a developmental block at the pro-B cell stage. The loss of TRPM7 kinase activity alone did not affect the proportion of peripheral mature B cells or the development of B cells in the bone marrow. However, supplementation with a high concentration of extracellular Mg2+ partially rescued the development of TRPM7-deficient B cells in vitro. Thus, our findings identify a critical role for TRPM7 ion channel activity in B cell development.

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