Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1002/eji.202048654 |
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| Title (Primary) | Plasma membrane Ca2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca2+ homeostasis in mice |
| Author | Korthals, M.; Tech, L.; Langnaese, K.; Gottfried, A.; Hradsky, J.; Thomas, U.; Zenclussen, A.C.; Brunner-Weinzierl, M.C.; Tedford, K.; Fischer, K.-D. |
| Source Titel | European Journal of Immunology |
| Year | 2021 |
| Department | IMMU |
| Volume | 51 |
| Issue | 3 |
| Page From | 594 |
| Page To | 602 |
| Language | englisch |
| Topic | T9 Healthy Planet |
| Supplements | https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Feji.202048654&file=eji4935-sup-0001-SuppMat.pdf |
| Keywords | B cells; Ca2+; PMCA1; PMCA4; development |
| Abstract | The amplitude and duration of Ca2+ signaling is crucial for B-cell development and self-tolerance; however, the mechanisms for terminating Ca2+ signals in B cells have not been determined. In lymphocytes, plasma membrane Ca2+ ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca2+ 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 Ca2+, elevated levels in ER stores, and reduced Ca2+ clearance. These findings show that the PMCA1 isoform alone is required to ensure normal B-cell Ca2+ signaling and development, which may have implications for therapeutic targeting of PMCAs and Ca2+ in B cells. |
| Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=29589 |
| Korthals, M., Tech, L., Langnaese, K., Gottfried, A., Hradsky, J., Thomas, U., Zenclussen, A.C., Brunner-Weinzierl, M.C., Tedford, K., Fischer, K.-D. (2021): Plasma membrane Ca2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca2+ homeostasis in mice Eur. J. Immunol. 51 (3), 594 - 602 10.1002/eji.202048654 |
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