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

Gotru, Sanjeev Kiran; Gil-Pulido, Jesus; Beyersdorf, Niklas; Diefenbach, Andreas; Becker, Isabelle C.; Vogtle, Timo; Remer, Katharina; Chubanov, Vladimir; Gudermann, Thomas; Hermanns, Heike M.; Nieswandt, Bernhard; Kerkau, Thomas; Zernecke, Alma und Braun, Attila (2018): Cutting Edge: Imbalanced Cation Homeostasis in MAGT1-Deficient B Cells Dysregulates B Cell Development and Signaling in Mice. In: Journal of Immunology, Bd. 200, Nr. 8: S. 2529-2534

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-1767
• Sprache: Englisch