Genome-wide analyses and functional profiling of human NK cell lines

Natural killer (NK) cell lines, including YTS, NK92, NK3.3, and NKL, represent excellent models for the study of human natural killer cells. While phenotypic and functional differences between these cell lines have been reported, a multi-parametric study, encompassing genomic, phenotypic, and functional assays, has not been performed. Here, using a combination of techniques including microarray and copy number analyses, flow cytometry, and functional assays, we provide in-depth genetic, functional, and phenotypic comparison of YTS, NK92, NK3.3, and NKL cell lines. Specifically, we found that while the cell lines shared similarities in enrichment of growth and survival pathways, they had differential expression of 557 genes, including genes related to NK cell development, survival, and function. In addition, we provide genetic and phenotypic analyses that demonstrate distinct developmental origins of NK92, YTS, and NKL cell lines. Specifically, NK92 has a phenotype associated with the CD56^bright NK cell subset, while both YTS and NKL appear more CD56^dim-like. Finally, by classifying cell lines based on their lytic potential, we identified genes differentially expressed between NK cell lines with high and low lytic function. Taken together, these data provide the first comprehensive genetic, phenotypic, and functional analyses of these commonly used NK cell lines and provides deeper understanding into their origins and function. This will ultimately improve their use as models for human NK cell biology.