Cutting Edge: Antibody-Dependent Memory-like NK Cells Distinguished by FcRγ Deficiency

Abstract Because NK cells lack gene-recombination machinery and are thought to be relatively short-lived, it is unclear whether NK cells can mount long-term effective recall responses to reinfections by diverse pathogens. In this article, we report that FcRγ-deficient NK cells, which we recently identified and termed g−NK cells, possess distinct memory features directed by FcR-mediated Ab-dependent target recognition. The presence of g−NK cells was associated with prior human CMV (HMCV) infection, yet g−NK cell responses were not restricted to HCMV-infected target cells. In the presence of virus-specific Abs, g−NK cells had greatly enhanced functional capabilities, superior to conventional NK cells, and were highly responsive to cells infected with either HCMV or HSV-1. Remarkably, the g−NK cell subset persisted long-term at nearly constant levels in healthy individuals. Therefore, FcRγ deficiency distinguishes an Ab-dependent memory-like NK cell subset with enhanced potential for broad antiviral responses.