The phenomenon of idiotypy or individual antigenic specificity is one of the most fascinating in immunology (1-3). Clearly, this phenomenon appears to be intimately linked to the two major problems of the immune system: the origin of antibody diversity and the regulation of the immune system (4).It has frequently been assumed that idiotypy could be explained by the somatic mutation theory. Different idiotypes were considered to be different somatic variants, appearing from very similar germ-line genes. However results from our laboratory (the Laboratory of Animal Physiology, Universit6 Libre de Bruxelles, Rhode-SaintGen~se, Belgium) and from the Pasteur Institute, Paris (4-11) indicate that, in fact, the total idiotypic repertoire is more or less the same in all rabbits and mice, with exceptions that have been discussed elsewhere (7). Briefly, these conclusions stem from experiments in which it was possible to elicit the synthesis of a specific idiotype in a randomly chosen animal. The rationale behind the experiment was suggested by network concepts (4,(12)(13)(14). If we suppose that rabbit X, which does not express idiotypes from rabbit 1, nevertheless contains silent lymphocyte clones precommitted to the synthesis of idiotypes from rabbit 1, it should be possible to relieve these silent clones from suppression by raising immunity against suppressor cells. In principle, specific suppressors should bear autoanti-idiotypic receptors. Therefore, conventional anti-idiotypic antibodies to anti-peptidoglycan antibody (Abl) 1 (denoted Ab2) were raised, purifed, and injected into other rabbits for the synthesis of anti.anti-idiotypic antibodies (Ab3). Rabbits who were making Ab3 were then injected with the original antigen. Using several antigenic systems, the data show that: (a) After injection of antigen, nearly all the rabbits synthesized antibodies that were idiotypically crossreactive with the starting Abl (denoted Abl'). (b) Although the bulk of Ab3 did not recognize antigen, Ab3 and Ab 1' shared some idiotypic specificities because anti-antianti-idiotypic antibodies (Ab4) also recognized Abl and Abl' antibodies. (c) Ab4 behaved like Ab2 and diversity did not seem to increase along the chain of immunization.These data suggest clearly that suppression is dominant in the immune response.* Supported by grants from the Belgian Government. t Recipient of a doctoral fellowship from I. R. C. I. A. Z Abbreviations used in this paper: Abl, anti-peptidoglycan antibody(ies); Abl', antibody(ies) that were cross-reactive with the starting Abl; Ab2, anti-idiotypic antibody(ies) to Abl; Ab3, anti-anti-idiotypic antibody(ies); Ab4, anti-anti-anti-idiotypic antibody(ies); Abl-F1, Abl produced by the offspring; BSA, bovine serum albumin; PBS, phosphate-buffered saline. 1024 j. ExP. MED.
