Specific antigen/antibody complexes induce the in vivo production of a parallel set of nonantigen-binding idiotype-positive antibodies.

Immune complexes prepared with the polysaccharide antigen (PnC) extracted from Streptococcus pneumoniae R36a and two different PnC-specific antibodies were found to differ in their regulatory properties depending on the isotype of the antibody. Thus, complexes formed in antibody excess with TEPC15 (IgA) were suppressive whereas complexes formed with 96-G (IgG3) antibodies enhanced the IgM response to PnC. During the course of these studies, we found that little or no PnC-specific IgG antibody was induced during the response to PnC coupled to sheep red blood cells (PnC-SRBC). Interestingly, however, immunization with 96-G/PnC complexes either alone or with PnC-SRBC resulted in the induction of IgG3 antibodies that express the T15 idiotype (Id) but which do not bind PnC. This unique IgG3 response occurred after injection of 96-G/PnC complexes formed in antibody excess but not when complexes were formed in antigen excess. The Id+ nonspecific IgG3 response peaked on day 5 and could be activated with 96-G/PnC complexes but not with free PnC antigen. The Id+ nonspecific response was not due to polyclonal activation of IgG3 production since there was no difference in IgG3 levels in mice injected with 96-G/PnC complexes with those injected with PnC-SRBC. Finally, mice that had been suppressed for expression of the T15 Id by neonatal injection of anti-Id antibody were able to produce Id+-unspecific IgG3 antibody after immunization with 96-G/PnC complexes, further suggesting that Id+ IgG3 was produced by different clones than those that usually comprise the antibody response to PnC. The results suggest that the formation of IgG immune complexes during an immune response may result in stimulation of idiotypically related clones thus resulting in degeneracy of the immune response.