Suppression or Augmentation of the Antihapten Response in Mice by Antibodies of Different Specificities

We have measured the production by (C57 x CBA)F(1) mice of hapten-binding antibody in response to a standard dose of 50 microg of alum-precipitated NIP(12)-CG and the influence on this response of the prior administration of hyperimmune antisera raised against the homologous conjugate, the carrier globulin alone, the hapten conjugated to a non-cross-reactive carrier (NIP(4)-OA), or a related hapten (NP) coupled to CG. The homologous antiserum was strongly immunosuppressive; a dose capable of binding about 1% of the administered hapten caused significant suppression. High doses of anticarrier serum caused significant but modest suppression (about 50%); low doses had no effect. High doses of the serum prepared against NIP(4)-OA suppressed the 19 day response by more than 97%, while 100-1,000 times lower doses caused the response to be elevated to about double the control level. The antibodies responsible for immunosuppression could be removed from this serum, as could the NIP-binding antibodies, by absorption with NIP coupled through ethylenediamine to insoluble Sepharose. The ability of this serum to augment the response was not reduced by such absorption. Augmenting antibodies could be removed by absorption with HOP-BSA-Sepharose. Thus, immunosuppression and augmentation are functions of two different populations of antibody. The former are specific hapten-binding antibodies, the latter seem to be directed against new antigenic determinants created by coupling any of the family of haptens through lysine to protein carriers. In support of this contention, it was observed that rabbit antiserum to NP-CG, after absorption with CG-Sepharose, augmented the response of mice to standard immunization with NIP(12)-CG. Female mice produced significantly more NIP-binding antibody than did males.