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 idiotype 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.