Myeloma-induced immunosuppression: a multistep mechanism.

Hosts of plasma cell tumors have a depressed primary antibody response. We have investigated the ability of cell homogenates and culture fluids from short-term cultures of spleen cells and tumor cells of mice bearing the MOPC-315 plasmacytoma to suppress the in vivo primary antibody response to sheep red blood cells. The homogenates and culture fluids of both MOPC-315 spleen cells and tumor cells suppress the antibody response in a dose-dependent manner. Culture fluids of spleen cells from tumor-bearing mice contain a 10,000- to 20,000-dalton immunosuppressive factor. Culture fluids of non-adherent tumor cells contain a high m.w. suppressor. Injection of the high m.w. tumor suppressive factor into normal mice induces the expression or appearance of host cells that secrete the 10,000- to 20,000-dalton immunosuppressor. The tumor suppressive factor, but not the spleen factor, causes an alteration of lymphocyte membranes such that the anti-DNP activity of the MOPC-315 myeloma protein can be detected on the circulating lymphocytes of injected mice.