Origin and function of suppressor macrophages in myeloma

Hosts of plasma cell tumors exhibit a unique pattern of immune impairment: their ability to mount a primary antibody response is depressed but their T-dependent cellular immune responses are normal. The studies reported here describe the mechanism by which plasma cell tumors in murine hosts depress antibody production; they show that at least two factors and a macrophage (Mφ) mediate plasmacytoma-induced immunosuppression. One factor, the plasmacytoma (PC) factor is produced by malignant plasma cells; it is noncytotoxic, cannot pass through a membrane which retains molecules > 30,000 and can induce normal peritoneal Mφ to produce an immunosuppressive molecule designated PIMS (plasmacytoma-induced macrophage substance). PIMS, the second factor required in this pathway, is produced by Mφ from the spleens of plasmacytoma-bearing mice and by normal murine macrophages cultured with malignant plasma cells or with the PC-factor contained in the medium in which malignant plasma cells have grown. PIMS has a m.w. < 6000 to 8000, is noncytotoxic, is capable of suppressing the primary antibody response of normal spleen cells cultured in vitro, and has no effect on the proliferative response of normal spleen cells to phytohemagglutinin. Thus, malignant plasma cells produce a factor (PC-factor) that induces Mφ to produce an immunosuppressive molecule (PIMS) that suppresses antibody production. The possibility that this phenomenon is reflective of a normal immunoregulatory pathway is discussed.