Selective elimination of idiotype-binding cells in vivo by a drug-idiotype conjugate demonstrates the functional significance of these cells in immune regulation.
A receptor-specific cytotoxic drug delivery system has been used to eliminate idiotype-binding cells in vivo to ascertain the possible functional significance of these cells in regulating the humoral immune response to dextran. Protein M104E, a mouse myeloma protein that binds dextran, expresses a private idiotope that is present on a significant proportion of the normal dextran-specific antibody repertoire. Immunocompetent cells that bind and internalize M104E idiotype-bearing molecules were eliminated by the intravenous administration of a single dose of cytosine arabinonucleoside conjugated to purified M104E protein. The administration of this cytotoxic drug-idiotype conjugate had a profound effect upon the expression of the M104E idiotype in euthymic but not in athymic BALB/c mice following immunization with dextran. In euthymic mice, the depletion of the idiotype-binding cells resulted in a marked elevation in the level of M104E idiotype present in the immune sera. Moreover, treated but not control mice developed idiotype-positive molecules that did not bind dextran. These results demonstrate the functional significance of idiotype-binding cells in the regulation of individual clonotypes during an immune response.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000917:Antibody Formation; D003561:Cytarabine / Q000008:administration & dosage; D003911:Dextrans / Q000276:immunology; D007130:Immunoglobulin Idiotypes; D000922:Immunotoxins / Q000633:toxicity*; D051379:Mice; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D003911:Dextrans; D007130:Immunoglobulin Idiotypes; D000922:Immunotoxins; D003561:Cytarabine