Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival Academic Article uri icon

abstract

  • 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.

authors

  • Viant, Charlotte
  • Guia, Sophie
  • Hennessy, Robert J
  • Rautela, Jai
  • Pham, Kim
  • Bernat, Claire
  • Goh, Wilford
  • Jiao, Yuhao
  • Delconte, Rebecca
  • Roger, Michael
  • Simon, Vanina
  • Souza-Fonseca-Guimaraes, Fernando
  • Grabow, Stephanie
  • Belz, Gabrielle T
  • Kile, Benjamin T
  • Strasser, Andreas
  • Gray, Daniel
  • Hodgkin, Phillip D
  • Beutler, Bruce
  • Vivier, Eric
  • Ugolini, Sophie
  • Huntington, Nicholas D

publication date

  • 2017