Simultaneous complementary idiotypic responses: absence of reciprocal regulation

Complementary antibodies, i.e. antibodies having combining site structures which are at least partially directed against each other, were induced in A/He mice by immunization with phosphorylcholine (Pc) coupled to keyhole limpet hemocyanin or with the Pc-binding IgA myeloma protein, HOPC-8 (H8). Both responses were monitored by enumerating plaque-forming cells and assaying serum antibody levels to Pc and H8. Prior immunization with H8 markedly suppressed subsequent immunization with Pc and vice versa; neither plaque-forming cell response was diminished, however, when mice were immunized simultaneously with Pc and H8. Experiments were designed to determine if the absence of reciprocal regulation was due to change in idiotypes. This was determined by measuring inhibition of plaque formation using complementary antibody. Plaque formation by cells was equally inhibited by high dilutions of the appropriate complementary antibody whether cells were from mice immunized with one, the other, or both antigens. Thus, the absence of regulation could not be accounted for by emergence of different idiotypes. Interestingly, sera from mice immunized to have high responses to both antigens were relatively ineffective in inhibiting plaque formation or suppressing immunization to Pc. However, such sera contained complexes of the complementary antibodies; apparently antibody to Pc in such sera quenches or neutralizes the activity of anti-H8 antibody. But the formation of complexes, at least measurable levels of circulating complexes, must be a result rather than the cause for the absence of reciprocal regulation, since regulation was also absent when immunization to Pc was manipulated so that responses were too low to result in detectable levels of circulating antibody to Pc. It is proposed that simultaneous complementary responses may occur in nature to other antigens and antibodies, and that such simultaneous responses may cause pathologic changes.