Inhibition of human natural killer cell activity by polyclonal IgM

Pretreatment of effector cells with normal human IgM induced strong dose-dependent inhibition of NK activity. The degree of inhibition by normal IgM was stronger than that induced by monomeric IgG, which has previously been reported to be a negative regulator of NK activity. For 100% inhibition, 1.1 × 10⁻⁶ M of IgM was required, whereas 66.6 × 10⁻⁶ M of IgG was needed to abolish NK activity. This inhibitory property of polyclonal IgM appeared to be localized in the Fc region of the molecule, and also was significantly reduced upon mild reduction of disulfide bonds. Monoclonal IgM purified from sera of five patients with Waldenström's macroglobulinemia and tested in parallel with normal IgM lacked or had a decreased capacity to inhibit the cytotoxic reaction. As with IgG, IgM interfered mainly with the lytic event, after binding of effector cells to target cells. The inhibition by IgM appeared to be a direct effect on NK cells, since similar effects were observed with purified large granular lymphocytes as with non-adherent lymphocytes. These results indicate a new mechanism for negative regulation of NK cells and suggest the presence of Fcμ receptors on these effector cells.