Our ongoing research is concerned with the regulation of immunity by complementary idiotypes expressed on Igs and B and T cell receptors. Specific suppression is produced by immunization of A/He mice with the phosphorylcholine (Pc) binding IgA myeloma protein secreted by the plasmocytoma HOPC-8 (H8). Such actively immunized mice are unresponsive to immunization with Pc containing antigens. Conversely, A/He mice actively immunized with Pc are unresponsive to immunization with H8. The process of suppression makes tolerant or eliminates mature B cells of the suppressed clone. Presumably, specific unresponsiveness mediated by a prior complementary response must occur in nature and be disadvantageous to the individual under some circumstances. If this is so, then the objective is to devise ways to suppress the prior response and rescue the suppressed response. Sublethal irradiation temporarily eliminates mature lymphocytes involved in suppression. following irradiation, treatment with antibody of the specificity produced by the suppressed clone neutralizes remaining complementary antibody or cells and also tolerizes or eliminates regenerating lymphocytes bearing comlementary receptors. In this way the passively given antibody permits regeneration of the suppressed clone. Recovery is slow, requiring 1 to 2 months, but is idiotype-specific. Treatment with irradiation alone or idiotype alone is totaly ineffective. The capability for suppressing one response and then rescuing an autogenous complementary response may be a clinical objective for treating some autoimmune diseases and cancer. The present model provides a conceptual basis for achieving this objective.
