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Cutting Edge: Imbalanced Cation Homeostasis in MAGT1-Deficient B Cells Dysregulates B Cell Development and Signaling in Mice.

Sanjeev Kiran GotruJesus Gil-PulidoNiklas BeyersdorfAndreas DiefenbachIsabelle C BeckerTimo VögtleKatharina RemerVladimir ChubanovThomas GudermannHeike M HermannsBernhard NieswandtThomas KerkauAlma ZerneckeAttila Braun
Published in: Journal of immunology (Baltimore, Md. : 1950) (2018)
Cation homeostasis, in relation to various immune-suppressive diseases, is a novel field of investigation. Recently, patients with a loss-of-function mutation in magnesium transporter 1 (MAGT1) were reported to present a dysregulated Mg2+ homeostasis in T lymphocytes. Using Magt1-knockout mice (Magt1-/y ), we show that Mg2+ homeostasis was impaired in Magt1-/y B cells and Ca2+ influx was increased after BCR stimulation, whereas T and NK cell function was unaffected. Consequently, mutant B cells displayed an increased phosphorylation of BCR-related proteins differentially affecting protein kinase C activation. These in vitro findings translated into increased frequencies of CD19+ B cells and marginal zone B cells and decreased frequencies of plasma cells among CD45+ splenocytes in vivo. Altogether, our study demonstrates for the first time, to our knowledge, that abolished MAGT1 function causes imbalanced cation homeostasis and developmental responses in B cells. Therefore, this study might contribute to a further understanding of B cell-related pathologies.
Keyphrases
  • protein kinase
  • acute lymphoblastic leukemia
  • ionic liquid
  • healthcare
  • induced apoptosis
  • type diabetes
  • metabolic syndrome
  • wild type
  • cell death
  • oxidative stress
  • endoplasmic reticulum stress
  • high fat diet induced