Anticarbohydrate antibodies (Abl) were isolated from a rabbit hyperimmunized with Micrococcus lysodeikticus and injected into allotype-matched rabbits in order to obtain specific anti-iodiotypic antibodies (Ab2). Ab2 was isolated by means of a Sepharose column coupled to the anticarbohydrate antibodies and was injected into two allotypematched rabbits. These latter rabbits produced specific antianti-idiotypic antibodies (Ab3) probably sharing idiotypic specificities with Abl. However, these Ab3 did not react with the antigenic carbohydrate moiety of bacteria. The two rabbits that had produced Ab3 were then immunized with M. lysodeikticus and synthesized anticarbohydrate antibodies (Abl') bearing idiotypic specificities similar to those of Abl. The immune repertoire which is effectively expressed in one individual depends not only on the antigenic stimulation but also on the previous idiotypic history of the individual. These data support the concept that the immune system is a functional idiotypic network.As a rule, in response to the same antigen, different individuals from the same species express different subsets of the total antibody repertoire of the species, with each subset bearing different idiotypic specificities (1-7) (these antibodies will be referred to as Abl). Idiotypic similarities were observed only in certain idiotypic systems (5,8) and were only partial with two main kinds of exceptions: (i) some rabbit families or some inbred strains of mice immunized with certain antigens synthesize antibodies with very similar idiotypic specificities (9-11); and (ii) very similar idiotypic specificities are often found among different antibody subpopulations present in the serum of a single individual immunized with a single antigen (12)(13)(14)(15)(16)(17)(18)(19)(20).The V domains of anti-idiotypic antibodies (which will be called Ab2) might themselves function as antigens and therefore elicit the synthesis of anti-anti-idiotypic antibodies (which will be referred to as AbS). These AbS might elicit the synthesis of Ab4, and so on. If Sepharose (21). The main fraction of anti-CHO antibodies from rabbit 2975 was eluted from the immunoadsorbent with 5% glucose in phosphate-buffered 0.15 M NaCl (Pi/NaCl), pH 7.5. Ab2 anti-idiotypic antisera were raised in allotype-matched rabbits.Allotypes tested were al, a2, a3, b4, b5, b6, b9, c7, c21, e14, dlI, and d12. Purified anti-CHO antibodies from rabbit 2975 (Abl) were polymerized with glutaraldehyde as described (22) and injected into six allotype-matched rabbits. Injections of 1 mg of AbI emulsified in complete Freund's adjuvant twice a week during 1 month was followed by the injection of 1 mg of AbI intravenously. Abl (1 mg) in incomplete Freund's adjuvant was then injected once a week. Ab2 from rabbit II (2238) were purified by means of a Sepharose column to which 200 mg of Ab had been coupled. Twenty milliliters of serum 2238 (Ab2) was passed through the column. After extensive washing, bound proteins were eluted with glycine-HCI, pH 2.2, and their i...

The amino acid sequence of fragments obtained by cyanogen bromide cleavage of the mu-chain of a human gammaM-globulin is homologous to the NH(2)-terminal sequences of the gamma-chain of human and rabbit gammaG-globulins and is related to that of human light chains. This supports the hypothesis that light and heavy chains evolved from a common ancestral gene.

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.

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Variation and conservation in the primary structure of human lambda light chains is revealed by complete amino acid sequence of three Bence Jones proteins. These proteins differ in amino acid sequence in from 38 to 48 positions; they are of unequal length in the amino-terminal half of the chain but have identical sequence in the last 105 amino acids.