IgG subclass and vaccination stimulus determine changes in antigen specific antibody glycosylation in mice

5 years ago

IgG subclass and vaccination stimulus determine changes in antigen specific antibody glycosylation in mice

Anja Schaffert, Anja Lux, Roland Lang, Daniela Kao, Falk Nimmerjahn, Friedrich Altmann

Immunoglobulin G (IgG) glycosylation can modulate antibody effector functions. Depending on the precise composition of the sugar moiety attached to individual IgG glycovariants either pro- or anti-inflammatory effector pathways can be initiated via differential binding to type I or type II Fc-receptors. However, an in depth understanding of how individual IgG subclasses are glycosylated during the steady state and how their glycosylation pattern changes during vaccination is missing. To monitor IgG subclass glycosylation during the steady state and upon vaccination of mice with different T-cell dependent and independent antigens, tryptic digests of serum, and antigen-specific IgG preparations were analyzed by reversed phase-liquid chromatography-mass spectrometry. We show that there is a remarkable difference with respect to how individual IgG subclasses are glycosylated during the steady state. More importantly, upon T-cell dependent and independent vaccinations, individual antigen-specific IgG subclasses reacted differently with respect to changes in individual glycoforms, suggesting that the IgG subclass itself is a major determinant of restricting or allowing alterations in specific IgG glycovariants. Depending on the type of activation and costimulation, B cells develop into plasma blasts and plasma cells and produce IgG antibodies of different subclasses. These individual IgG subclasses have a distinct glycosylation profile, suggesting that IgG class switching and glycosylation are linked.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201747208