Plasma membrane Ca 2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca 2+ homeostasis in mice.

Autor: Korthals M; Institute for Biochemistry and Cell Biology, Otto-von-Guericke University, Magdeburg, Germany., Tech L; Institute for Biochemistry and Cell Biology, Otto-von-Guericke University, Magdeburg, Germany., Langnaese K; Institute for Biochemistry and Cell Biology, Otto-von-Guericke University, Magdeburg, Germany., Gottfried A; Institute for Biochemistry and Cell Biology, Otto-von-Guericke University, Magdeburg, Germany., Hradsky J; Institute for Biochemistry and Cell Biology, Otto-von-Guericke University, Magdeburg, Germany., Thomas U; Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Zenclussen AC; Experimental Obstetrics and Gynecology, Otto-von-Guericke University, Magdeburg, Germany., Brunner-Weinzierl MC; Department of Pediatrics, Otto-von-Guericke University, Magdeburg, Germany., Tedford K; Institute for Biochemistry and Cell Biology, Otto-von-Guericke University, Magdeburg, Germany., Fischer KD; Institute for Biochemistry and Cell Biology, Otto-von-Guericke University, Magdeburg, Germany.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2021 Mar; Vol. 51 (3), pp. 594-602. Date of Electronic Publication: 2020 Nov 16.
DOI: 10.1002/eji.202048654
Abstrakt: The amplitude and duration of Ca 2+ signaling is crucial for B-cell development and self-tolerance; however, the mechanisms for terminating Ca 2+ signals in B cells have not been determined. In lymphocytes, plasma membrane Ca 2+ ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca 2+ from the cell through the plasma membrane. We report here that Pmca4 (Atp2b4) KO mice had normal B-cell development, while mice with a conditional KO of Pmca1 (Atp2b1) had greatly reduced numbers of B cells, particularly splenic follicular B cells, marginal zone B cells, and peritoneal B-1a cells. Mouse and naïve human B cells showed only PMCA1 expression and no PMCA4 by western blot, in contrast to T cells, which did express PMCA4. Calcium handling was normal in Pmca4 -/- B cells, but Pmca1 KO B cells had elevated basal levels of Ca 2+ , elevated levels in ER stores, and reduced Ca 2+ clearance. These findings show that the PMCA1 isoform alone is required to ensure normal B-cell Ca 2+ signaling and development, which may have implications for therapeutic targeting of PMCAs and Ca 2+ in B cells.
(© 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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