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Science Immunology  06 Sep 2019:
Vol. 4, Issue 39, eaaz2439
DOI: 10.1126/sciimmunol.aaz2439

Abstract

During pregnancy, mothers generate di-galactosylated IgGs that cross the placenta more readily and provide the fetus and the newborn infant with antibodies optimized for NK cell–mediated antibody-dependent cellular cytotoxicity.

Women undergo many changes in pregnancy, some obvious and others not so apparent, but all geared toward providing the optimal conducive environment for the rapidly developing fetus. During pregnancy, maternal immunity is suppressed to avoid fetal rejection. After birth, the newborn is dependent on parental protection and maternally provided nutrition. Time and some exposure to the environment are required for the maturation of the immune system in the infant. Although some maternal IgA is transferred to the fetus after birth through breast milk and colostrum, it is the previous transfer of IgG across the placental barrier during pregnancy that most potently provides the infant protection from the hostile world after birth. Although all four human IgG subclasses have the potential to neutralize, IgG1 and IgG3 are generally more potent in terms of complement fixation and the activation of phagocytes and NK cells. It has long been assumed that maternal IgGs during pregnancy are much the same as IgGs in nonpregnant adults, but a study by Jennewein et al. has now shown that one of the changes that occurs in pregnancy is that maternal IgGs of all subclasses are made much sweeter in the context of protection of the fetus and the infant.

The Fc portion of human IgG has a single N-glycan that tends to lose terminal sialic acid and pre-terminal galactose moieties in the context of infection and inflammation. The authors used a systems serology approach wherein they examined the glycosylation profiles and functions of IgG Fc regions in pregnant women and controls. They found that during pregnancy the Fc N-glycan of maternal IgGs is largely di-galactosylated. These di-galactosylated IgGs bind more readily to FcRn, the Fc receptor that transfers IgG across the placenta during pregnancy and also extends the half-life of IgG after birth. Di-galactosylated IgG also more readily binds to FcγR3A on NK cells, thereby more efficiently mediating anti-viral defense by ADCC. Pregnancy therefore results in the optimization of IgGs to better cross the placental barrier and, when in the fetus or in the infant, to also positively tune antiviral defense mechanisms.

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