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Type: Journal article
Title: Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival
Author: Viant, C.
Guia, S.
Hennessy, R.
Rautela, J.
Pham, K.
Bernat, C.
Goh, W.
Jiao, Y.
Delconte, R.
Roger, M.
Simon, V.
Souza-Fonseca-Guimaraes, F.
Grabow, S.
Belz, G.
Kile, B.
Strasser, A.
Gray, D.
Hodgkin, P.
Beutler, B.
Vivier, E.
et al.
Citation: Journal of Experimental Medicine, 2017; 214(2):491-510
Publisher: Rockefeller University Press
Issue Date: 2017
ISSN: 0022-1007
Statement of
Charlotte Viant, Sophie Guia, Robert J. Hennessy, Jai Rautela, Kim Pham ... Benjamin T. Kile ... et al.
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.
Keywords: Killer Cells, Natural
Rights: © 2017 Viant et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http ://www .rupress .org /terms /). After six months it is available under a Creative Commons License (Attribution–Noncommercial– Share Alike 4.0 International license, as described at https ://creativecommons .org /licenses /by -nc -sa /4 .0 /).
DOI: 10.1084/jem.20160869
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