Myeloma-Specific Antibodies: Studies of Their Properties and Their Relationship to Tumor Immunity

The anti-idiotypic antibodies (a-Id315) induced in BALB/c mice by immunization with the dinitrophenyl (DNP)-binding, isologous myeloma protein produced by MOPC-315 were analyzed by double antibody radioimmunoassay to determine time of appearance, levels, heavy chain class, inhibitability with DNP-hapten, and relationship to MOPC-315 transplantation resistance. Following 200 µg of RA-315 per immunization, a-Id315 activity and MOPC-315 transplantation resistance were detected after the second of five weekly immunizations, and both increased after each subsequent immunization. After five weekly immunizations, individual sera from 180 mice were found to bind from 50 to 860 µg of 125I-RA-315 per ml. Approximately 95% of the a-Id315 detected after five weekly immunizations belonged to the IgG1 class, and the remaining 5% was IgG2a. Between 80 and 100% of the a-Id315 binding was inhibited by 3 × 10-3 M 2,4-DNP-L-lysine. Immunization schedules using increasing amounts of immunogen, from 5 to 200 µg, or increasing numbers of immunizations, from 1 to 4 showed that the induction thresholds for a-Id315 activity and the myeloma graft resistance were indistinguishable. When mice immunized with 200 µg of RA-315 weekly for 5 weeks were challenged with numbers of MOPC-315 cells sufficient to overcome transplantation resistance in 50 to 80% of the mice, none of the a-Id315 features analyzed differentiated resistant from nonresistant mice. Passive administration of a-Id315 serum did not influence the growth of MOPC-315 cells in normal syngeneic hosts. These observations suggest that the mechanism of idiotype-specific transplantation resistance observed in a-Id315-producing hosts probably involves more than the a-Id315 antibodies alone.