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J OUDIN

Publications and source records attributed to J OUDIN.

At least 19 recordsLinked to original sources

A STUDY OF RABBIT GAMMA-GLOBULIN ALLOTYPY BY MEANS OF HETEROIMMUNIZATIONS.

Representatives of two species, the chicken and the goat, were immunized by injection with Freund's adjuvant, of specific precipitates prepared from the antisera of rabbits with various allotypic specificities. The precipitation reactions of the resulting antisera with normal rabbit sera were studied in liquid and in gellified media. In these reactions the isotypic specificity and often one or the other of the allotypic specificities of rabbit gamma-globulin were involved. It was always easier to obtain antibodies against the specificities controlled by the alleles of locus b (Ab4, Ab5, Ab6) than of locus a (Aa1, Aa2, Aa3). The precipitation reaction of antibodies against a specificity of the a series could always be inhibited by an excess (nearly always moderate) of a serum lacking this specificity. A similar inhibition of the antibodies against the specificities of the b series was often impossible, especially if the antiserum had been collected after a second injection of immunizing material. The reactions of 58 Ab4(+) sera with a goat anti-Ab4 serum and of 28 Ab5(+) sera with a chicken anti-AbS serum were studied in gel tubes (simple diffusion). The constant observation of two precipitation zones due respectively to two types of molecules, Ab4(+) and Ab4(-) (or Ab5(+) and Ab5(-)), indicated the existence of an appreciable number of Ab4(-) or Ab5(-) molecules, even in supposed homozygotes. In the latter rabbits Ab4(-) or Ab5(-) molecules are b(-) molecules; i.e., molecules lacking the specificities of the b series. Measurements of the distances between the two zones in the reaction of 72 sera revealed significant differences between sera of individuals of the same phenotype, as well as systematic differences not only between sera of homozygotes and of heterozygotes, but also between heterozygotes of different genotypes. These measurements were used to evaluate the ratio of concentrations of the two types of molecules detected by each of the two antisera. The occurrence of b(-) molecules in every one of the fairly large number of sera studied indicates a new aspect of the heterogeneity of gamma-globulin. Although detected by means of allotypy, this heterogeneity is not dependent upon factors which vary with individuals. These results are discussed in connection with what is known of the structure of gamma-globulin.

Animals↗

STUDIES ON THE RELATIONSHIP OF ALLOTYPIC SPECIFICITIES TO ANTIBODY SPECIFICITIES IN THE RABBIT.

Purified antibodies against three different antigens and haptens (ovalbumin, dinitrophenol, and Type II pneumococcal polysaccharide) were prepared from specific precipitates from the antisera of several rabbits. The reactions of these preparations with antisera against the allotypic specificities carried by each of the animals forming the antibodies were used to compare the relative concentrations of molecules bearing each specificity in the different solutions of antibodies from each rabbit. These relative concentrations appeared to vary greatly from one preparation to another, although all the allotypic specificities carried by each animal were found in all the preparations of antibodies from that animal. The interpretation of these results is discussed.

Animals↗

[Allotypy].

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Antigens↗

Allotypy of rabbit serum proteins. I. Immuno-chemical analysis leading to the individualization of seven main allotypes.

The injection into one rabbit (with Freund's adjuvants) of a specific precipitate made with antibodies from the serum of another rabbit is usually followed by the appearance in the serum of the first rabbit of antibodies which precipitate the serum of certain rabbits but not of others. It was found that the antigen (or one of the antigens) concerned in the reaction of these anti rabbit serum antibodies with rabbit sera had an antibody function, and was therefore a protein. It was concluded that at least one serum protein antigen, the specificity of which so far has been considered to be uniform throughout the animal species, can instead be present in different individuals as different forms or allotypes with somewhat different antigenic specificities. A large number of rabbit sera were allowed to react with a large number of rabbit immune sera. The gel method of immunochemical analysis made it possible to enumerate the allotypes that took part in each reaction. In addition, the technique mainly used (simple diffusion in separate tubes) made it possible to recognize the presence of one given allotype by the mere aspect of the precipitation zone in the reaction of one suitable immune serum with any serum in which the concerned allotype occurred. Neighboring reactions of sera, in contact with each other and with the suitable immune serum, in suitable cells easily constructed in the laboratory, were carried out occasionally and, each time, their results agreed with the previous identification. The analysis of the reactions in tubes lead to a list of seven allotypes designated by a, b, c, d, e, f, and g, of which two or more (e not included) were contained in almost every serum. The specific conditions necessary for antibody formation against an allotype are its absence from the serum of the immunized animal and, except in the case of cross-reactivity, its presence in the immunizing material. When these necessary conditions are fulfilled for several allotypes at the same time, their competition in the immunization seems to favor the allotype present at the highest concentration. The individuality of six of the listed allotypes has been discussed independently of the part of their specificity that may be common to all the allotypes of one given protein antigen in all the individuals of the same animal species. A cross-reaction of the anti f rabbit antibodies with allotype g has been observed. When two allotypic specificities were detected in one serum, attempts were made to find whether they were carried by two allotypes, i.e. by two distinct kinds of molecules, instead of being the manifestation of two "allotypic patterns" present on the same molecules. The presence of several allotypes in the immune sera made it often impossible to find definitive answers in this regard. However, for a limited number of cases of two allotypic specificities present in one serum, it could be demonstrated that at least a large proportion (if not the totality) of the two allotypes were independent of each other. No sign of a systematic coexistence of two allotypic patterns on the same molecules has been observed to date.

Animals↗

Allotypy of rabbit serum proteins. II. Relationships between various allotypes: their common antigenic specificity, their distribution in a sample population; genetic implications.

The relationships between six of the seven allotypes or families of allotypes (a, b, c, d, f, g) described in the preceding paper, have been studied from the standpoints of (1) their antigenic specificities, (2) their mutual influence on the limitation of their respective frequencies, and (3) their genetic control. Although the six different allotypes (or families) react quite differently with the rabbit antisera, at least five of them react identically with a guinea pig antiserum. Therefore, a large portion of the antigenic specificity of these allotypes, distinct from their allotypic specificity, is uniform in all the individuals of the rabbit species and is termed for this reason "isotypic specificity." In the early period of the rabbit's life, allotypes may be found in the serum, which are not determined by the genotype of the individual, but are directly transmitted by the mother. The allotypes of the antigenic species of globulin studied in this paper, which were synthesized by the young animal, did not appear in its serum before a certain period of time. Allelic relationships between the genes which control allotypes were indicated by, (1) the absence of certain kinds of groupings of the allotypes, which limits the number of allotypic formulas in the population sample studied, (2) dosage effects, the concentration of certain allotypes (drawn from the penetration of the zones in gel tubes) being smaller in supposed heterozygotes than in supposed homozygotes, (3) the results of the analysis of the sera of a number of rabbits and of their parents. Eight of the different antigenic substances studied in this paper (allotype e excluded) appear to be allotypic forms of what would have been considered to be a uniform protein antigen. They may be classified as follows: a first group which contains two allotypes b and d and a family of two allotypes c and c' apparently controlled by three allelic genes b c d, c and c' being controlled by the same gene; a second group which contains two allotypes a and f and a family g, g' apparently controlled by three allelic genes a f g. There are reasons to believe that this list is not complete, especially in the b c d group.

Alleles↗