Studies on the pathogenesis of an immune defect in multiple myeloma.
The reduced capacity of patients with multiple myeloma to respond to antigen challenge is well recognized. Response to antigen involves antigen recognition, cell proliferation, and synthesis and secretion of antibody. This study examines this sequence of events in peripheral blood lymphocytes from untreated and treated patients with myeloma, from individuals with benign monoclonal gammopathy, and from normal healthy donors. Antigen-binding capacity was assessed by testing the ability of lymphocytes to bind radio-labeled pneumococcal polysaccharide, tetanus toxoid, or diptheria toxin. The in vitro proliferative response to these antigens as well as to pokeweed mitogen and streptokinase-streptodornase was evaluated. The secretion of immunoglobulin in response to pneumococcal polysaccharide, tetanus toxoid, and pokeweed mitogen by 2-4 x 10(6) lymphocytes in 7-day cultures was determined. The effects of coculture of myeloma peripheral blood lymphocytes and normal peripheral blood lymphocytes on immunoglobulin production and mixed leukocyte reactions were explored. All myeloma patients had normal numbers (3-8/5,000 cells) of antigen-binding cells. However, most showed a diminished antigen-induced blast transformation as measured by uptake of [(125)I]5-iodo-2'-deoxyuridine in culture. Immunoglobulin production in response to specific antigen in myeloma lymphocytes was 30-80% less than in normal lymphocytes. Immunoglobulin synthesis and mixed leukocyte responses by normal peripheral blood lymphocytes could be suppressed by myeloma lymphocytes. Multiple suppressor populations were present. Thus, the immune defect in myeloma is beyond the antigen recognition step and involves both the proliferation of antigen-sensitive cells and immunoglobulin production. Further suppressive effects are imposed on normal cells, implying defects in immunoregulation in this disease.
D000328:Adult; D000368:Aged; D000941:Antigens; D001402:B-Lymphocytes / Q000276:immunology; D001666:Binding Sites, Antibody; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D037102:Lectins / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D008937:Mitomycins / Q000494:pharmacology; D009101:Multiple Myeloma / Q000150:complications / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D013296:Streptococcus pneumoniae; D013601:T-Lymphocytes / Q000276:immunology; D013745:Tetanus Toxoid / Q000494:pharmacology
D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D037102:Lectins; D008937:Mitomycins; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid