Analysis of the interaction of antibodies with immunoglobulin idiotypes on neoplastic B lymphocytes: implications for immunotherapy.
We have examined the reactions of a panel of nine monoclonal anti-idiotype antibodies with the surface immunoglobulin in situ on guinea pig L2C leukemic lymphocytes. Equilibrium binding constants were shown to range between 10(7) and 10(8) M-1 for univalent Fab' gamma fragments and between 10(8) and 10(9) M-1 for intact IgG. Saturation of the cell surface binding sites was achieved with 2.9 X 10(5) Fab' gamma molecules/cell and 1.2 X 10(5) IgG molecules/cell for each antibody, a result that is consistent with a bivalent mode of interaction for the IgG. Despite these overall similarities in binding characteristics antibodies showed striking differences in their ability to clear Ig from the cell surface by antigenic modulation in vitro. This suggested differences in the readiness with which the antibodies cross-linked neighboring surface Ig molecules. Such an interpretation was supported by differences in the times required to achieve bivalent binding at 0 degree C, and in the rates at which labeled antibody dissociated from the cell surface in the presence or absence of an excess of unlabeled antibody. The data are consistent with there being two functionally distinct types of anti-idiotype antibody: those that form predominantly intra-Ig bridges, with each antibody Fab being linked to an Fab on one target molecule ("monogamous" binding) and not favoring modulation; and those that form predominantly inter-Ig bridges ("bigamous" binding) and favor modulation. The nature of interaction is presumably dictated by the orientation of the particular idiotope concerned. This distinction could be of great importance in the therapeutic use of anti-idiotype to ablate B cell neoplasms.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology*; D001667:Binding, Competitive; D000939:Epitopes / Q000032:analysis; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000378:metabolism; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007167:Immunotherapy; D007942:Leukemia, Experimental / Q000276:immunology* / Q000628:therapy; D008657:Metabolic Clearance Rate; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D011947:Receptors, Antigen, B-Cell