AUTHOR=van de Bovenkamp Fleur S. , Derksen Ninotska I. L. , van Breemen Mariëlle J. , de Taeye Steven W. , Ooijevaar-de Heer Pleuni , Sanders Rogier W. , Rispens Theo 

TITLE=Variable Domain N-Linked Glycans Acquired During Antigen-Specific Immune Responses Can Contribute to Immunoglobulin G Antibody Stability

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00740

DOI=10.3389/fimmu.2018.00740

ISSN=1664-3224

ABSTRACT=<p>Immunoglobulin G (IgG) can contain <italic>N</italic>-linked glycans in the variable domains, the so-called Fab glycans, in addition to the Fc glycans in the C<sub>H</sub>2 domains. These Fab glycans are acquired following introduction of <italic>N</italic>-glycosylation sites during somatic hypermutation and contribute to antibody diversification. We investigated whether Fab glycans may—in addition to affecting antigen binding—contribute to antibody stability. By analyzing thermal unfolding profiles of antibodies with or without Fab glycans, we demonstrate that introduction of Fab glycans can improve antibody stability. Strikingly, removal of Fab glycans naturally acquired during antigen-specific immune responses can deteriorate antibody stability, suggesting <italic>in vivo</italic> selection of stable, glycosylated antibodies. Collectively, our data show that variable domain <italic>N</italic>-linked glycans acquired during somatic hypermutation can contribute to IgG antibody stability. These findings indicate that introducing Fab glycans may represent a mechanism to improve therapeutic/diagnostic antibody stability.</p>