Immunoregulatory role of maternal idiotypes. Ontogeny of immune networks.

Abstract

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.

Antibody Repertoire Development in Fetal and Neonatal Piglets. XI. The Relationship of Variable Heavy Chain Gene Usage and the Genomic Organization of the Variable Heavy Chain Locus

“…In swine, there is no known protein transfer from mother to fetus including Igs (32)(33)(34). Because maternal Igs can influence fetal immune responses (35,36) and presumably B cell selection and development, usage of certain VDJ rearrangements is independent of this influence in fetal piglets. Although it is known that certain porcine viruses can cross the placenta, the mechanism remains unknown.…”

Immune function across generations: integrating mechanism and evolutionary process in maternal antibody transmission

“…Thus, the duration of these maternal effects may far outreach the presence of maternally derived antibodies in offspring. Antibodies administered during the neonatal period of mammals influence the B-cell repertoire expressed after antigenic challenge later in life (mice: Strayer et al 1974;Wikler et al 1980;Rubinstein et al 1982;Elliott & Kearney 1992;rats: Lundin et al 1999). In some cases, maternal antibodies may even affect immune function across multiple generations.…”

Antibody Repertoire Development in Fetal and Neonatal Piglets. XX. B Cell Lymphogenesis Is Absent in the Ileal Peyer’s Patches, Their Repertoire Development Is Antigen Dependent, and They Are Not Required for B Cell Maintenance

“…Thus, using the piglet as a model to study the role of the IPP of artiodactyls is appropriate but more importantly permits improvements to the experimental design. The fetal B and T cell repertoires of both species develop without maternal influence and regulatory factors such as maternal IgG that are known to influence fetal immunological development in mice and rabbits (37)(38)(39)(40)(41). However, swine have multiple offspring (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), weigh ,2 kg at birth, and can be conveniently reared in GF isolators after their recovery by cesarean surgery where all environmental and maternal factors are thereafter controlled by the experimenter (41,42).…”