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Published on: May 22, 2016
The Emerging Importance of IgG Fab Glycosylation in Immunity
Fleur S van de Bovenkamp1, Lise Hafkenscheid2, Theo Rispens3
1Department of Immunopathology, Sanquin Research, 1066 CX Amsterdam, the Netherlands; Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands;
Abstract:
Human IgG is the most abundant glycoprotein in serum and is crucial for protective immunity. In addition to conserved IgG Fc glycans, ∼15-25% of serum IgG contains glycans within the variable domains. These so-called "Fab glycans" are primarily highly processed complex-type biantennary N-glycans linked to N-glycosylation sites that emerge during somatic hypermutation. Specific patterns of Fab glycosylation are concurrent with physiological and pathological conditions, such as pregnancy and rheumatoid arthritis. With respect to function, Fab glycosylation can significantly affect stability, half-life, and binding characteristics of Abs and BCRs. Moreover, Fab glycans are associated with the anti-inflammatory activity of IVIgs. Consequently, IgG Fab glycosylation appears to be an important, yet poorly understood, process that modulates immunity.
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