The CD16 and CD32b Fc-gamma receptors regulate antibody-mediated responses in mouse natural killer cells

Abstract Natural killer (NK) cells are innate lymphocytes capable of mediating immune responses without prior sensitization. NK express Fc-gamma receptors (FcγR) that engage the Fc region IgG. Studies investigating role FcγR on mouse have been limited due to lack specific reagents. In this study, we characterize expression and biological consequences activating through their FcγR. We demonstrate most CD16 receptor, a subset also inhibitory CD32b receptor. Critically, these FcγRs functional can modulate antibody-mediated responses. characterized mice with conditional knock-out alleles Fcgr3 (CD16) or Fcgr2b (CD32b) in lymphoid cell (ILC) lineage. did not reveal any developmental defects were responsive cross-linking receptors, cytokine stimulation, killing YAC-1 targets. Importantly, CD16-deficient failed induce antibody-directed cellular cytotoxicity (ADCC) antibody-coated B lymphomas vitro assays. addition, important using an vivo model cancer immunotherapy anti-CD20 antibody treatment lymphomas. This project was funded by fellowships from Burroughs Wellcome Fund (BWF) Cancer Research Institute O.A.A., grants Parker for Immunotherapy (PICI), NIH (AI068129 AI146581) L.L.L.