Influence of IgG and IgM receptor triggering on human natural killer cell cytotoxicity measured on the level of the single effector cell.

By using an agarose single cell cytotoxicity assay, in combination with rosetting with IgG- or IgM-coated ox red blood cells for detection of Fc receptors for IgG (Fc gamma R) or IgM (Fc muR), it was found that 60% of natural killer (NK) cells are Fc gamma R+ and 17% FcmuR+. This system was further used to investigate the consequence of FcmuR and FC gamma R triggering on NK killing as measured on the single effector cell level. It was found that stimulation of the Fc gamma R, but not the FCmuR, resulted in substantial NK inhibition. In order for NK cells to be inhibited by IgG-coated ox red blood cells, they must first be exposed to the IgG-containing complex prior to conjugation with the target. While exposure of the Fc gamma R to immune complexes can block up to 57% of NK activity, the particulate immune complexes do not interfere with binding of effector cells to targets. Modulation of Fc gamma R by capping at 37 degrees C does not interfere with the NK inhibition for up to 3 h, though after 20 h, when Fc gamma R+ cells are almost completely modulated, NK activity has fully returned. Although to a lesser extent, the soluble immune complex human transferrin-anti-transferrin also reduces NK cell activity when activating effector cell FC gamma R prior to target cell binding. Also, pretreatment of target cells with high concentrations of specific antibody toward membrane antigens can block NK activity while not inhibiting target cell binding as evidenced by anti-IgM IgG binding to Daudi cells. The regulatory influence of the Fc gamma R on the NK system is discussed in terms of other functions associated with this receptor and in terms of its possible biological significance.