T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies

Constanze Hess, André Winkler, Alexandra K. Lorenz, Vivien Holecska, Véronique Blanchard, Susanne Eiglmeier, Anna Lena Schoen, Josephine Bitterling, Alexander D. Stoehr, Dominique Petzold, Tim Schommartz, Maria M.M. Mertes, Carolin T. Schoen, Ben Tiburzy, Anne Herrmann, Jörg Köhl, Rudolf A. Manz, Michael P. Madaio, Markus Berger, Hedda WardemannMarc Ehlers

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind on immune cells. Recent studies have shown that pro- or antiinflammatory effector functions of IgG Abs are also regulated through their Fc N-linked glycosylation patterns. IgG Abs that are agalactosylated (nongalactosylated) and asialylated are proinflammatory and induced by the combination of T cell-dependent (TD) protein antigens and proinflammatory costimulation. Sialylated IgG Abs, which are immunosuppressive, and Tregs are produced in the presence of TD antigens under tolerance conditions. T cell-independent (TI) B cell activation via B cell receptor (BCR) crosslinking through polysaccharides or via BCR and TLR costimulation also induces IgG Abs, but the Fc glycosylation state of these Abs is unknown. We found in mouse experiments that TI immune responses induced suppressive sialylated IgGs, in contrast to TD proinflammatory Th1 and Th17 immune responses, which induced agalactosylated and asialylated IgGs. Transfer of low amounts of antigen-specific sialylated IgG Abs was sufficient to inhibit B cell activation and pathogenic immune reactions. These findings suggest an immune regulatory function for TI immune responses through the generation of immunosuppressive sialylated IgGs and may provide insight on the role of TI immune responses during infection, vaccination, and autoimmunity.

Original languageEnglish (US)
Pages (from-to)3788-3796
Number of pages9
JournalJournal of Clinical Investigation
Volume123
Issue number9
DOIs
Publication statusPublished - Sep 3 2013

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ASJC Scopus subject areas

  • Medicine(all)

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Hess, C., Winkler, A., Lorenz, A. K., Holecska, V., Blanchard, V., Eiglmeier, S., ... Ehlers, M. (2013). T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies. Journal of Clinical Investigation, 123(9), 3788-3796. https://doi.org/10.1172/JCI65938