Anti-idiotype antibody-dependent cell-mediated cytotoxicity (ADCC) against idiotype-bearing cells.
The present report demonstrates that cells expressing idiotypic determinants on their surfaces can be specifically destroyed by anti-idiotypic antibodies acting as inducers of antibody-dependent cell-mediated cytotoxicity. Lysis of surface-idiotype-positive hybridoma cells was effected by mouse spleen cells, mouse peritoneal cells, or human blood mononuclear cells, in the presence of anti-idiotypic antibodies. In order for lysis to occur, the simultaneous presence of Fc receptor-bearing cytotoxic cells and anti-idiotypic antibodies was required. Specificity of lysis was conferred by the anti-idiotypic antibody. Hybridoma cells expressing a different idiotype could not be lysed. Anti-idiotypic antibody-dependent cell-mediated cytotoxicity against 51Cr-labeled cells expressing a particular idiotype could be induced by the specific anti-idiotypic antibodies and inhibited by unlabeled idiotype-positive cells or by idiotype in a soluble form. Cytotoxicity could not be inhibited by the presence of bystander cells or monoclonal antibodies expressing a different idiotype. It is proposed that ADCC lysis of idiotype-positive cells has important implications for understanding the regulation of immune responses by an idiotype-anti-idiotype network. This cytolytic pathway provides an extremely specific and effective mode of control of idiotype-positive cells by anti-idiotype antibody. Previous observations that an intact Fc fragment was necessary for anti-idiotype antibodies to exert suppressive effects in vivo further support this hypothesis.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D002460:Cell Line; D005260:Female; D006801:Humans; D006825:Hybridomas / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes