Regulation of IgG Antibody-dependent Cellular Cytotoxicity in Vitro by IgM Antibodies.

Abstract

IgM antibodies reportedly either inhibit or induce antibody-dependent lymphocyte cytotoxicity (ADCC). Human lymphocytes lyse bovine erythrocytes (Eb) in the presence of IgM or IgG anti-Eb from rabbits. Of 20 IgM preparations (Sephadex G-200), were ADCC-active. IgG-dependent ADCC was inhibited by human IgG but not by IgM. IgM ADCC was inhibited by both IgG and IgM. The effector cells in IgM ADCC were a subpopulation of lymphocytes with distinct Fc receptors for both IgG and IgM. Most also had sheep erythrocyte receptors. Extensive purification of the ADCC-active IgM antibody preparations indicated that very small amounts of contaminating IgG anti-Eb were responsible for ADCC induction. When purified and ADCC -inactive IgM antibodies were mixed with suboptimal concentrations of IgG2 antibodies, a strong enhancement of ADCC was found. To achieve enhancement, the 2 antibody isotypes had to be present on the surface of the same target cells; the IgM effect was not due to the release of soluble ADCC-enhancing factors. Thus, in this system, IgM antibodies are not capable of inducing ADCC on their own. They enhance ADCC by improving the contactual interaction between target cells and a special subset of effector cells.