Allotypes, suppression

For unexplained reasons, there occurs an escape from the block in B cell maturation sometime between 18 and 30 months of age, and immunoglobulin levels rise rapidly to normal. This phenomenon resembles allotypic suppression in rabbits. A search for discordance in Gm alleles amongst the parents of affected infants or for the presence of Gm agglutinators in the mothers of affected infants revealed no significant differences from what would be expected by random events. 

The mechanism of Ig allotype suppression is not clear. The lack of experimental data concerning this problem forces us to limit ourselves to the more or less likely suggestions. In the first paper dealing with suppression of Ig synthesis by allotype antibodies it was reported that those rabbits suppressed to b having b b genotypes did not produce the b allotype in the lymphatic node and spleen, but possessed only the b" allotype. These preliminary histoimmunochemical investigations allowed, even then, the conclusion that suppression occurs on the cellular level and is based on a more complicated process than the simple neutralization of allotypes in the blood by injected antibodies (Dray, 1962). 

Another experiment bearing on the same question was carried out by suppression, with antiallotypic antiserum, of allotypic specificities in... 

Prenatal or early postnatal exposure to antiallotypic antibodies may suppress the appearance of the corresponding allotypic specificities. Such suppression has been accomplished in rabbits and in a particular strain of mice. 

The first experiments on suppression were reported by Dray and by Mage and Dray (212,213). Female rabbits of allotype lAlA k chain locus), were mated with bucks and were immunized during pregnancy with b5 immunoglobulin. The b offspring showed a greatly diminished serum concentration of b5, as compared to ordinary het-... 

Suppression of allotype has proven to be a powerful tool in im-munogenetic research. For example, suppression of rabbits homozygous... 

Harrison et al. showed that suppression of allotype b5 in homozygous rabbits was accompanied by a complete absence of circulating lymphocytes having membrane-bound b5 immunoglobulins (220). During recovery from suppression the appearance of b5 molecules in the serum was preceded by the appearance of lymphocytes with membrane-bound b5 molecules. Determinants on the lymphocyte surface were detected with fluorescent or I-labeled anti-b5 antibodies. 

The existence of strong idiotypic cross-reactions among different mice of the same strain, with respect to certain antigens, made it feasible to attempt suppression of a particular idiotype with antiidiotypic antiserum. This could be analogous to suppression of an allotype in heterozygous animals with antiallotypic antiserum (Chapter 9). The appearance of an idiotype, characteristic of anti-p-azophenylarsonate (anti-Ar) antibodies of A/J mice was suppressed for periods up to 5 months, in neonatal or adult A/J mice, by intraperitoneal administration of a saline solution of 2 or 4 mg of an IgG fraction of rabbit anti-D antiserum (103). It was shown that suppression is not caused by simple absorption of anti-Ar antibodies by the antiidiotypic antibodies injected. There was no concomitant suppression of the total antihapten response or of production of antibody to the protein carrier. 

Suppressive Action of Allotypic Antibodies on the Synthesis of Immunoglobulins 111... 

The suppression of the paternal allotype was induced in b b -progeny, not only through in utero (through the mother) immunization, but also when the progeny... 

The first attempt to suppress the synthesis of Ig allotypes in mice was unsuccessful. The majority of progeny from immunized mice mothers died, and surviving offspring demonstrated a normal concentration of the paternal allotype. However, Herzenberg successfully suppressed Ig synthesis with Ig-lb specificity, initially for short periods of time and then for the entire life of the mouse (Herzenberg, 1970). Recently, short-term suppression of Ig synthesis in mice was induced with the aid of antibodies to some of the determinants of the variable part of light polypeptide chains (Ruffmi et al., 1970). 

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