| First Author | Segawa K | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 48 | Pages | 12212-12217 |
| PubMed ID | 30355768 | Mgi Jnum | J:269290 |
| Mgi Id | MGI:6259488 | Doi | 10.1073/pnas.1814323115 |
| Citation | Segawa K, et al. (2018) Phospholipid flippases enable precursor B cells to flee engulfment by macrophages. Proc Natl Acad Sci U S A 115(48):12212-12217 |
| abstractText | ATP11A and ATP11C, members of the P4-ATPases, are flippases that translocate phosphatidylserine (PtdSer) from the outer to inner leaflet of the plasma membrane. Using the W3 T lymphoma cell line, we found that Ca(2+) ionophore-induced phospholipid scrambling caused prolonged PtdSer exposure in cells lacking both the ATP11A and ATP11C genes. ATP11C-null (ATP11C (-/y) ) mutant mice exhibit severe B-cell deficiency. In wild-type mice, ATP11C was expressed at all B-cell developmental stages, while ATP11A was not expressed after pro-B-cell stages, indicating that ATP11C (-/y) early B-cell progenitors lacked plasma membrane flippases. The receptor kinases MerTK and Axl are known to be essential for the PtdSer-mediated engulfment of apoptotic cells by macrophages. MerTK (-/-) and Axl (-/-) double deficiency fully rescued the lymphopenia in the ATP11C (-/y) bone marrow. Many of the rescued ATP11C (-/y) pre-B and immature B cells exposed PtdSer, and these cells were engulfed alive by wild-type peritoneal macrophages, in a PtdSer-dependent manner. These results indicate that ATP11A and ATP11C in precursor B cells are essential for rapidly internalizing PtdSer from the cell surface to prevent the cells' engulfment by macrophages. |
