Considerable attention has been devoted recently, to the genetically defined differences that may exist amongst the immunoglobulins of different individuals belonging to the same species. This phenomenon (allotypy), is not confined to the immuuoglobulins, but it is particularly in this field that the presence of genetical markers allows a deeper insight in different physiological or pathological processes that are related with the synthesis of these molecules. One of the more interesting questions that, on the basis of the genetic markers, have been raised with regards to the synthesis of the immunoglobulins is whether, in an individual heterozygous at a given locus, the products of two allelic genes are manufactured by different immunoglobulin-producing cells.Clear evidence for a differentiation of plasma cells with regards to the molecular classes (1, 2) or the antigenic type (3, 4) of the immunoglobulins that they produce has been obtained by immunofluorescence studies of human lymphoid tissues; when, however, this same method has been applied to the localization of gamma globulin allotypes in lymph node cells of heterozygous rabbits, then it was found (5) that the products (A4 and A5) 1 of two aUelic genes were almost regularly present in the same cell.As the results of Colberg and Dray (5) were complicated by the fact that the fluorochrome-conjugated antisera that had been used contained some of the antigenic determinants whose cellular localization was being studied, we decided to reinvestigate this problem with the use of antisera that did not react between themselves. In addition to the study of rabbits heterozygous at the b locus, we examined also animals heterozygous at the a locus and we have found
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The phenomenon of "anti-antibodies" of individual (idiotypic) specificity was first described by Kunkel et al. (1) as a result of the experiments in which heteroprecipitins against human antibodies were employed. A similar finding of idiotypic determinants within the same (rabbit) species was reported by Oudin and Michel (2) and Judepc, .ienfly by Gell and Kelus (3). The terms "idiotypie" specificity as well as "isotypic" and "allotypic" specificities were proposed by Oudin (4) as simple and logical: "Three kinds of antigenic speeificities with different genetic meanings may be distiuguished.., in immunoglobnlin.q... The isotypic speeificities are those which are uniform in all individuals of one animal species" (often referred to as species-specific determinants). "The allotypiv specificities are those which are different in different groups of individuals within the same species" (these are usually spoken of as stimulating isoantibodies, though we should prefer the term antiaUotypic antibodies). "The term/d/otyp/e specificities was chosen to designate antigenic specificities of immunoglobulins which are peculiar in two respects. Each of them is peculiar, first to antibodies against one given antigen, and secondly, to one individual or perhaps to one group of individuals, within which the idiotypic specificities of the antibodies against one antigen is not the same as it is in other individuals or groups." All these speeifieities may be demonstrable by heteroimmunization, although the isotypic specificities are dominant: the allotypie speeificities characteristic of many different kinds of molecule, or e.g. immtmoglobuin class, will be demonstrable best by intraspeeies (mouse into mouse, rabbit into rabbit etc.) immunization (see review by Kelus and Gell, reference 5). If pairs oI animals which are genetically alike with respect to their aUotypic constitution are cross-immunized with antibodies, the idiotypie specificities alone will be active in producing anti-antibodies(antiidiotypie antibodies). It should be noted however, as will be seen from the results described below, that unknown allotypic systems present in immunogiobulin classes can cause some complications. The work to be described is mainly devoted to the investigation of antiidiotypic antibodies and idiotypie determinants; these in our experience are strictly individual-specific and therefore the saving clause used in the quotation above from Oudin "or perhaps to one group of individuals"--may not be necessary. Fig. 1. illustrates diagrammatically the properties of antiidiotypic antibodies in the system we have used. For clarity, we retain in the description of our 215 on May 12, 2018 jem.rupress.org Downloaded from
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