摘要：SummaryAdaptive human natural killer (NK) cells display significantly enhanced responsiveness to a broad-range of antibody-bound targets through the engagement of CD16 compared to conventional NK cells, yet direct reactivity against tumor targets is generally reduced. Adaptive NK cells also display a distinct phenotype and differential expression of numerous genes, including reduced expression of signaling adapter FcRγ and transcription factor PLZF. However, it is unclear whether differential expression of specific genes is responsible for the characteristics of adaptive NK cells. Using CRISPR-Cas9, we show deletion of FcRγ in conventional NK cells led to enhanced CD16 responsiveness, abolished cell surface expression of natural cytotoxicity receptors, NKp46 and NKp30, and dramatically reduced responsiveness to K562 and Raji tumor cells. However, deletion of PLZF had no notable effects. These results suggest multiple roles for FcRγ and identify its deficiency as an important factor responsible for the functional and phenotypic characteristics exhibited by adaptive NK cells.Graphical AbstractDisplay OmittedHighlights•FcRγ deletion leads to increased cytokine production in response to CD16 stimulation•FcRγ deletion abolishes cell surface expression of NKp46 and NKp30•FcRγ deletion results in reduced responsiveness to K562 and Raji cells•PLZF deletion does not change responsiveness to CD16 and cytokine stimulationMolecular Biology; Immunology; Cancer
