Cutting edge: Antibody-dependent memory-like NK cells distinguished by FcRγ deficiency

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 FcRg-deficient NK cells, which we recently identified and termed g^-NK cells, possess distinct memory features directed by FcR-mediated Abdependent 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 virusspecific 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.