title: Proapoptotic Bim regulates antigen-specific NK cell contraction and the generation of the memory NK cell pool after cytomegalovirus infection.
abstract: Apoptosis is critical for the elimination of activated lymphocytes after viral infection. Proapoptotic factor Bim (Bcl2l11) controls T lymphocyte contraction and the formation of memory T cells after infection. Natural killer (NK) cells also undergo antigen-driven expansion to become long-lived memory cells after mouse cytomegalovirus (MCMV) infection; therefore, we examined the role of Bim in regulating the MCMV-driven memory NK cell pool. Despite responding similarly early after infection, Bcl2l11(-/-) Ly49H(+) NK cells show impaired contraction and significantly outnumber wild-type (WT) cells after the expansion phase. The inability to reduce the effector pool leads to a larger Bcl2l11(-/-) NK memory subset, which displays a less mature phenotype (CD11b(lo), CD27(+)) and lower levels of NK cell memory-associated markers KLRG1 and Ly6C. Bcl2l11(-/-) memory NK cells demonstrate a reduced response to m157-mediated stimulation and do not protect as effectively as WT memory NK cells in an MCMV challenge model. Thus, Bim-mediated apoptosis drives selective contraction of effector NK cells to generate a pool of mature, MCMV-specific memory cells.
authors: Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143.
authors: Gundula
authors: G
authors: Min-Oo
authors: Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143.
authors: Natalie A
authors: NA
authors: Bezman
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
authors: Sharline
authors: S
authors: Madera
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
authors: Joseph C
authors: JC
authors: Sun
authors: Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143 Lewis.Lanier@ucsf.edu.
authors: Lewis L
authors: LL
authors: Lanier
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology*; D000072224:Bcl-2-Like Protein 11; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000943:Antigens, Differentiation; D000956:Antigens, Viral; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins