The mechanisms of antibody-dependent killing mediated by lymphoid and myeloid cells are distinct based on different divalent cation requirements.
To further understand the mechanism(s) of antibody-dependent cell-mediated cytotoxicity (ADCC) by various effector populations, we have examined the extracellular Ca++ and Mg++ requirements for ADCC performed by lymphocytes, monocytes, polymorphonuclear leukocytes and peritoneal macrophages. We have used the anti-Fc gamma R-bearing hybridoma cell lines (HC) as self directed targets for ADCC to analyse the triggering ability of each of the three defined Fc gamma R; Fc gamma RI, Fc gamma RII, and Fc gamma RIII. Lymphocyte killing of the anti-Fc gamma RIII bearing HC (HC 3G8) was Ca++ dependent, but Mg++ independent. In contrast, monocytes and PMN killed the anti-Fc gamma RI- (HC 32) and the anti-Fc gamma RII- (HC IV.3) bearing HC in a Mg++-dependent, Ca++-independent fashion. In addition, freshly prepared monocytes were able to kill HC 3G8 in a Mg++-dependent, Ca++-independent fashion, indicating that low levels of Fc gamma RIII may be functionally detected on monocytes. Peritoneal macrophages were able to kill all three of the anti-Fc gamma R bearing HC in a Mg++-dependent, Ca++-independent fashion. Thus, the same target is lysed by myeloid cells in the presence of Mg++ without Ca++ and by lymphoid cells in the presence of Ca++ without Mg++. These results suggest that at least two distinct mechanisms of ADCC exist that depend on the type of effector cell mediating antibody-dependent killing and not necessarily on the Fc gamma R type triggered.
Graziano
R F
RF
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03756.
Erbe
D V
DV
Fanger
M W
MW
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity; D000943:Antigens, Differentiation / Q000276:immunology; D001667:Binding, Competitive; D018821:CD18 Antigens; D002118:Calcium / Q000502:physiology; D002413:Cations, Divalent; D002460:Cell Line; D005260:Female; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008274:Magnesium / Q000502:physiology; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D002413:Cations, Divalent; D011961:Receptors, Fc; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion; D008274:Magnesium; D002118:Calcium