IGG M-COMPONENTS IN ACTIVE MYELOMA PATIENTS INDUCE A DOWN-REGULATION OF NATURAL-KILLER-CELL ACTIVITY

Natural killer cell activity and related cell surface markers of perip heral blood lymphocytes were studied in 73 patients with multiple myel oma, 25 with monoclonal gammopathy of undetermined significance, and 2 0 normal controls. Natural killer cell number was significantly higher in both multiple myeloma and monoclonal gammopathy patients than in c ontrols, whereas the natural killer activity of multiple myeloma patie nts was inversely related to their disease status. Incubation of perip heral blood lymphocytes or natural killer cells with IgG myeloma prote ins purified from several patients induced a down-modulation of basic natural killer activity. This inhibitory effect of monoclonal IgG was dose dependent and significantly stronger in patients with active (at diagnosis and at relapse) than stable multiple myeloma or in normal co ntrols. Addition of exogenous recombinant interleukin-2 restored natur al killer cell activity against K562 target cells, indicating that nat ural killer cells were able to recover their functions. However, recom binant interleukin-2-stimulated natural killer cells were responsive t o downmodulation of monoclonal IgG. These data suggest that impaired n atural killer cell function in active multiple myeloma is caused by th e inhibitory effect of M-component.