| First Author | Korthals M | Year | 2021 |
| Journal | Eur J Immunol | Volume | 51 |
| Issue | 3 | Pages | 594-602 |
| PubMed ID | 33098669 | Mgi Jnum | J:302967 |
| Mgi Id | MGI:6508634 | Doi | 10.1002/eji.202048654 |
| Citation | Korthals M, et al. (2021) Plasma membrane Ca(2+) ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca(2+) homeostasis in mice. Eur J Immunol 51(3):594-602 |
| abstractText | 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 naive 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. |
