Myeloma-Specific Transplantation Resistance: a Requirement for Complete Freund's Adjuvant Stimulation of Effectors

Abstract

BALB/c mice immunized with purified BALB/c myeloma protein M315 produce anti-idiotypic antibody (a-Id315), directed predominantly to the binding site of that protein, and are resistant to challenge with the corresponding plasmacytoma, MOPC-315. Previous studies showed that the induction thresholds and decay patterns for the two activities were very similar; in the present study, the two activities were separated. Mice that received their initial exposure to M315 in incomplete Freund's adjuvant (IFA), instead of complete Freund's adjuvant (CFA), produced a-Id315 but transplantation resistance was greatly reduced in magnitude. With respect to IgG subclass distribution and hapten inhibitability by ε-DNP-L-lysine, the specific ligand of M315, the antibody was indistinguishable from that produced when CFA was used as adjuvant. Although the binding capacity of the antibody was in general lower than that produced with the standard protocol with CFA, examination of the binding capacities of sera from individual IFA-immunized mice demonstrated that the diminished resistance was not strictly correlated with the level of binding capacity. When a-Id315 activity was monitored in the sera of M315-immunized mice after tumor cell challenge, it was found that IFA-immunized mice maintained antibody levels as well as CFA-immunized mice. In mice developing tumors during the monitoring period, activity was maintained until 2 to 4 days before the detection of palpable tumors or M315 protein in the serum. The results suggest that although a-Id315 may be involved in the mediation of the myeloma-specific transplantation resistance, other elements of the immune system, which are stimulated by CFA, are required for the full expression of resistance.