title: Novel molecular mechanism for generating NK-cell fitness and memory.
abstract: The mammalian immune system has been traditionally subdivided into two compartments known as the innate and the adaptive. T cells and B cells, which rearrange their antigen-receptor genes using the RAG recombinase, comprise the adaptive arm of immunity. Meanwhile, every other white blood cell has been grouped together under the broad umbrella of innate immunity, including NK cells. NK cells are considered innate lymphocytes because of their rapid responses to stressed cells and their ability to develop without receptor gene rearrangement (i.e. in RAG-deficient mice). However, new findings implicate a critical function for RAG proteins during NK-cell ontogeny, and suggest a novel mechanism by which controlled DNA breaks during NK-cell development dictate the fitness, function, and longevity of these cells. This review highlights recent work describing how DNA break events can impact cellular differentiation and fitness in a variety of cell types and settings.
authors.affiliation: Immunology Program and Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Karo
authors.affiliation: Immunology Program and Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sun
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D053960:DNA Breaks; D004260:DNA Repair / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D045567:VDJ Recombinases / Q000276:immunology*
chemical_list: D045567:VDJ Recombinases
keywords: Memory cells; NK cells; Recombination; VDJ