Cutting Edge: Imbalanced Cation Homeostasis in MAGT1-Deficient B Cells Dysregulates B Cell Development and Signaling in Mice
| Autor: | Attila Braun, Niklas Beyersdorf, Timo Vögtle, Heike M. Hermanns, Alma Zernecke, Jesus Gil-Pulido, Andreas Diefenbach, Vladimir Chubanov, Thomas Gudermann, Thomas Kerkau, Bernhard Nieswandt, Sanjeev K. Gotru, Katharina A. Remer, Isabelle C. Becker |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male T-Lymphocytes Immunology Antigens CD19 Lymphocyte Activation CD19 03 medical and health sciences Mice Antigen Cations Cation homeostasis medicine Immunology and Allergy Animals Homeostasis Cation Transport Proteins B cell Protein Kinase C Mice Knockout B-Lymphocytes biology Chemistry breakpoint cluster region Marginal zone Cell biology Hematopoiesis Killer Cells Natural Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure biology.protein Phosphorylation Leukocyte Common Antigens Calcium Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 200(8) |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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