| First Author | Viant C | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 2 | Pages | 491-510 |
| PubMed ID | 28057804 | Mgi Jnum | J:240424 |
| Mgi Id | MGI:5883381 | Doi | 10.1084/jem.20160869 |
| Citation | Viant C, et al. (2017) Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival. J Exp Med 214(2):491-510 |
| abstractText | Natural killer (NK) cells are innate lymphoid cells with antitumor functions. Using an N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a strain with an NK cell deficiency caused by a hypomorphic mutation in the Bcl2 (B cell lymphoma 2) gene. Analysis of these mice and the conditional deletion of Bcl2 in NK cells revealed a nonredundant intrinsic requirement for BCL2 in NK cell survival. In these mice, NK cells in cycle were protected against apoptosis, and NK cell counts were restored in inflammatory conditions, suggesting a redundant role for BCL2 in proliferating NK cells. Consistent with this, cycling NK cells expressed higher MCL1 (myeloid cell leukemia 1) levels in both control and BCL2-null mice. Finally, we showed that deletion of BIM restored survival in BCL2-deficient but not MCL1-deficient NK cells. Overall, these data demonstrate an essential role for the binding of BCL2 to BIM in the survival of noncycling NK cells. They also favor a model in which MCL1 is the dominant survival protein in proliferating NK cells. |
