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

Publisher Website
Google Scholar
Abstract
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 (FcγR) or IgM (FcμR), it was found that 60% of natural killer (NK) cells are FcγR+ and 17% FcμR+. This system was further used to investigate the consequence of FcμR and FcγR triggering on NK killing as measured on the single effector cell level. It was found that stimulation of the FcγR, but not the FcμR, 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 FcμR 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 Fcγ R by capping at 37°C does not interfere with the NK inhibition for up to 3 h, though after 20 h, when FcγR+ 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 FcγR 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 FcγR on the NK system is discussed in terms of other functions associated with this receptor and in terms of its possible biological significance.
Keywords