Monoclonal antibodies to idiotype inhibit in vitro growth of human B-cell lymphomas.
The effect of monoclonal antibodies (MoAbs) recognizing idiotype, IgM heavy chain, and IgD heavy chain on the in vitro DNA synthesis of five randomly selected leukemic human low-malignancy B-cell lymphomas was investigated. In three lymphomas of different histologic subtype, low concentrations of anti-idiotypic (anti-Id) MoAb completely inhibited spontaneous 3H-thymidine uptake of T-cell-- and monocyte-depleted tumor cells, whereas two other tumors were not affected. Maximal inhibition of DNA synthesis was achieved at MoAb concentrations ranging from 0.5 to 250 micrograms/mL and required crosslinking by bivalent antibody but not Fc-mediated effects. While two anti-IgM MoAbs were similarly efficient as anti-Id MoAb in inhibition of DNA synthesis, two anti-IgD MoAbs had no effect. Thus, surface IgD molecules seemed to be neither able to deliver inhibitory signals themselves nor to antagonize IgM-mediated signals when simultaneously crosslinked by anti-Id MoAb. Leukocyte differentiation antigen expression, IgM density, and IgM/IgD ratio on the surface of lymphoma cells did not distinguish between sensitive and resistant tumors. In vitro tumor cell survival was differently affected by prolonged incubation with anti-Id antibody. In a centrocytic lymphoma and an immunocytoma, but not in a chronic lymphocytic leukemia, suppression of 3H-thymidine uptake persisted after removal of MoAb and tumor cell viability decreased during prolonged incubation with anti-Id MoAb. These results suggest that direct inhibitory signaling via surface IgM may contribute to anti-Id MoAb-mediated tumor regression in certain human B-cell lymphomas.
van Endert
P M
PM
Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg.
Heilig
B
B
Hämmerling
G J
GJ
Moldenhauer
G
G
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000276:immunology*; D002470:Cell Survival; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010835:Phytohemagglutinins; D011961:Receptors, Fc / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D010835:Phytohemagglutinins; D011961:Receptors, Fc