The mechanism of immune suppression in BALB/c mice bearing the plasmacytoma TEPC-183

Abstract

Mice bearing transplantable plasmacytomas have an immune defect closely resembling the defect of patients with multiple myeloma. They have a severe impairment of the primary immune response to both T-dependent and T-independent antigens, yet their secondary immune response is much less impaired. The aim of this series of experiments was to document the primary immune response of mice bearing the plasmacytoma TEPC-183. Healthy mice and mice bearing the reported non-immunosuppressive tumour MOPC-104E were used as controls. The response to chicken red blood cells (CRBC) was documented by a complement dependent cytotoxicity assay for IgM and an antibody dependent cellular cytotoxicity assay for IgG. The defect was shown to affect both the primary IgM and IgG responses to CRBC but could be overcome either by increasing the antigen dose or by using Freund's complete adjuvant together with antigen. Immunological memory was also impaired in TEPC-183-bearing mice. In a second series of experiments the primary immune responses of immunologically deprived syngeneic mice were measured after they had been reconstituted with cells from normal or tumour-bearing mice. Lymphocyte reconstitution experiments were carried out in mice which had been irradiated with 950 R. Lymphoid preparations from TEPC-183-bearing mice were as effective as those from healthy controls in reconstituting primary immune responses. When mice were deprived of macrophage function using large doses of horse red blood cells, macrophage preparations from normal mice were able to restore primary immune responsiveness partially. However, macrophages from TEPC-183-bearing mice were unable to bring about such restoration. It is concluded that the impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183 is due to a macrophage rather than lymphocyte abnormality.