2 DIFFERENT FC-GAMMA RECEPTOR-DEPENDENT CYTOTOXIC MECHANISMS TRIGGERED BY MONOCLONAL IMMUNOGLOBULINS

It is known that the receptors for the Fc portion of IgG molecules (Fc-gamma-R) are widely distributed in cells of the immune system. The expression of Fc-gamma-R enables monocytes and neutrophils to destroy antibody-coated target cells through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. In addition, the interaction of immune complexes or aggregated IgG with monocytes or neutrophils led to the lysis of nonsensitized target cells in a process known as nonspecific cytotoxicity (NSC). Despite that ADCC and NSC are both triggered through Fc-gamma-R, the cytolytic mechanism involved in each reaction is different. In this paper we analyze the ability of human monoclonal IgG1, IgG2, IgG3 and IgG4 to induce ADCC and NSC. Our results demonstrate that each IgG subclass is able to induce both, NSC and ADCC, mediated by monocytes or neutrophils, indicating that there is no correlation between IgG subclass specificity and the ability to activate both mechanisms.