Divergent effects of Fc gamma RIIIA ligands on the functional activities of human natural killer cells in vitro

Eur J Immunol. 1996 Jun;26(6):1199-203. doi: 10.1002/eji.1830260602.


The Fc gamma receptor (R)IIIA (CD 16) plays an important role in regulating the cytotoxic and non-cytotoxic functions of human natural killer (NK) cells. Some anti-CD 16 monoclonal antibodies (mAb) have been shown to stimulate NK activity, while human monomeric (m) IgG induces dose-dependent inhibition of NK activity. To explore further these interactions mediated via Fc gamma RIIIA, purified NK cells were cultured for 2-3 days in the presence of mIgG, 3G8 mAb, interleukin-2 (IL-2) or a combination of mIgG or 3G8 with IL-2. Binding of mIgG or 3G8 to Fc gamma RIIIA induced divergent effects of functions of cultured NK cells: 3G8 mAb + IL-2 induced dose-dependent inhibition of proliferation attributable to apoptosis; in contrast, mIgG + IL-2 significantly increased NK cell proliferation. Incubation of NK cells in the presence of mIgG up-regulated expression of surface activation markers (CD69, IL-2R alpha, ICAM-1), cytotoxicity, cytokine production (IL-1 beta, IFN-gamma and TNF-alpha) and release of soluble IL-2R. Thus, mIgG binding to Fc gamma RIIIA induced stimulatory signals in human NK cells, leading to up-regulation of IL-2R alpha expression, cell proliferation and cytokine release.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / metabolism
  • Apoptosis
  • Cell Division / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Humans
  • Immunoglobulin G / immunology
  • Interleukin-2 / pharmacology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation*
  • Receptors, IgG / physiology*
  • Receptors, Interleukin-2 / metabolism
  • Solubility


  • Antigens, CD
  • Cytokines
  • Immunoglobulin G
  • Interleukin-2
  • Receptors, IgG
  • Receptors, Interleukin-2