Changes in subclass-specific IgG Fc glycosylation associated with the postnatal maturation of the murine immune system

Gabriela Barrientos,Mislav Novokmet,Gordan Lauc,Melanie L Conrad,Yahia Almousa,Siniša Habazin

doi:10.1038/s41598-020-71899-7

Abstract

Early postnatal life is characterized by a critical time period in which the developing neonatal immune system transitions from passive immunity, induced by protective maternal antibodies, to the competence of a fully functioning immune system. The inflammatory capability of both maternal and neonatal antibodies is governed by N-linked glycosylation of the Fc region, and though this has been examined extensively in adults, there is currently little information regarding antibody glycosylation patterns during early postnatal life. To characterize the murine IgG Fc glycosylation profile during early life, we used nano-LC-ESI-Qq-TOF mass spectrometry analysis to assess subclass specific Asn-297 glycosylation patterns in the serum of BALB/c mice from 5–60 days of age. From birth to adulthood, we observed a decline in proinflammatory Fc glycosylation in all IgG subclasses. This was shown by significantly reduced agalactosylated and monogalactosylated structures combined with increased sialylation after weaning at 45 and 60 days of age. This information indicates that the transition between neonatal life and adulthood in mice is accompanied by reduction of inflammatory IgG antibodies. Our study contributes to a growing body of literature indicating the importance of IgG Fc glycosylation and its association with inflammation during different life stages.

Highlights

Antibodies act as key players in the adaptive immune response by binding to specific antigens and facilitating their phagocytosis by innate immune cells
Our study demonstrated that during postnatal development, IgG1 and IgG3 subclasses were characterized by a steady decrease in proinflammatory agalactosylated and monogalactosylated structures with increasing age, with concurrent increases in alpha-1,3-galactosylated Immunoglobulin G (IgG) in all antibody subclasses
Our results are in agreement with human studies showing that children between the ages of 6 and 25 years showed decreasing agalactosylated and increasing digalactosylated total IgG glycans corresponding with increasing age[19,22,23]

Summary

Introduction

Antibodies act as key players in the adaptive immune response by binding to specific antigens and facilitating their phagocytosis by innate immune cells. Of note, during the postnatal period analysed in our study, male and female offspring showed no differences in the kinetics of IgG1 glycosylation (see Supplementary Fig. 1).

Results

Conclusion