Adaptive antibody diversification through N -linked glycosylation of the immunoglobulin variable region

• DOI: 10.1073/pnas.1711720115
• Publication Date: 2018-02-05T20:21:44Z
• Authors: Fleur S. van de B...; Ninotska I. L. De...; Pleuni Ooijevaar-...; Karin A. van Schie; Simone Kruithof; Magdalena A. Berk...; C. Ellen van der ...; Hanna IJspeert; Mirjam van der Burg; Ann Gils; Lise Hafkenscheid; René E. M. Toes; Yoann Rombouts; Rosina Plomp; Manfred Wuhrer; S. Marieke van Ham; Gestur Vidarsson; Theo Rispens
• Keywords: B-Lymphocytes; 0303 health sciences; Glycosylation; variable domain glycosylation; Antibody Affinity; Immunoglobulin Variable Region; Fab glycosylation; Antibodies, Monoclonal; EMC MM-02-72-01; Antibodies; 3. Good health; Arthritis, Rheumatoid; 03 medical and health sciences; Immunoglobulin G; Humans; antibody diversification; Autoantibodies

Significance

Structural variation of antibodies is generally defined in terms of amino acid composition, neglecting posttranslational modifications such as N -linked glycosylation. Little is known about the role of the glycans that are present in about 15% of variable domains. However, recent studies suggest that variable domain glycans exhibit distinct patterns according to (patho)physiological conditions, and can have immunomodulatory effects. Here we highlight a physiological role for variable domain glycans that is predetermined in the germline antibody repertoire: We show that variable domain N -linked glycans are acquired during somatic hypermutation at positions predisposed in the germline and may be positively selected during affinity maturation, representing an additional mechanism of secondary antibody diversification that contributes to the extent of the B-cell antibody repertoire.