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Current Trends in Immunology   Volumes    Volume 2 
Abstract
Role of asymmetric IgG antibodies in fetal maintenance
Ricardo A. Margni, Ileana Malan Borel
Pages: 153 - 163
Number of pages: 11
Current Trends in Immunology
Volume 2 

Copyright © 1999 Research Trends. All rights reserved

ABSTRACT

Immune response develops with the production of two IgG class antibody types, namely precipitating or symmetric antibodies capable of fixing complement and clearing antigen, and co-precipitating or asymmetric antibodies, whose immunochemical and biological behavior is entirely different. The latter antibodies possess an asymmetric structure due to a mannose-rich oligosaccharide moiety present in only one of the two Fab regions in the molecule. The combination of the corresponding antibody site with the antigen is sterically hindered by the oligosaccharide group so that the molecule behaves functionally as univalent, unable to activate effector functions, such as complement fixation, phagocytosis and cytotoxicity, among others.

Since such findings are common to all animal species, asymmetric molecules may well play a major physiological role. Here we analyzed the participation of asymmetric antibodies in one of the controversial immunological issues which is the maintenance of the fetus in the maternal uterus.

We have demonstrated that asymmetric antibodies are produced during pregnancy. They are found both in serum and in the IgG bound to placenta with specific activity to paternal antigens. Placental supernatants from normal pregnancy induced an increase in the proportion of asymmetric antibodies synthesized by a hybridoma. On analysing the placental cells responsible of this effect it was attributable to trophoblasts and to a lesser extent to the remaining cells (including lymphocytes). These observations suggest that placental factors are relevant for fetal protection and may play a leading role in the immuno equilibrium between mother and fetus, thus regulating antibody synthesis by the mother during gestation.

As regards the effect of pregnancy on asymmetric molecule synthesis, against antigens related or not to the fetus, virgin rats, rats paired with allogeneic males, and virgin rats inoculated with placental supernatant were inoculated with ovalbumin. The percentage of asymmetric molecules, with or without specificity for such antigens, was evaluated in obtained sera. The results showed that the percentage of asymmetric molecules with or without anti-ovalbumin activity was increased considerably in samples originating from pregnant rats or rats to whith placental supernatant had been transferred, similarly as in those presenting paternal anti-lymphocyte activity.

This finding led us to identify the molecule responsible of this effect. It was confirmed that one of the factors that participate in IgG glycosylation was IL-6.

It is interesting to note that purified placental factors, acting as modulators of the glycosylation of synthesized IgG antibodies, may be useful for therapeutic use, especially in cases of recurrent spontaneous abortions, where an increase in biologiically activated precipitating antipaternal antibodies has been demostrated, in tissue transplants and in autoimmune diseases, where preferential synthesis of specific blocking antibodies could prove protective.
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