T cell–independent B cell activation induces immunosuppressive sialylated IgG antibodies
Constanze Hess, … , Hedda Wardemann, Marc Ehlers
Constanze Hess, … , Hedda Wardemann, Marc Ehlers
Published August 27, 2013
Citation Information: J Clin Invest. 2013;123(9):3788-3796. https://doi.org/10.1172/JCI65938.
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Research Article Immunology

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

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 (non-galactosylated) 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.

Authors

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 Wardemann, Marc Ehlers

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Figure 1

TI antigen–specific B cell activation induces IgM and IgG Abs and reduces a subsequent antigen-induced DTH response.

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TI antigen–specific B cell activation induces IgM and IgG Abs and reduce...
(A) Experimental approach. WT mice were injected i.p. with PBS or 50 μg of TNP-Ficoll, TNP-LPS, TNP-LPS in CFA, TNP-LPS in alum, NP-Ficoll, TNP-BSA, or TNP-BSA in CFA on day –12. DTH was induced by i.p. injection of TNP-OVA in alum on day 0 and OVA in the right footpad on day 14. (B) Anti-TNP IgM, total IgG, and IgG1, IgG2c, IgG2b, and IgG3 subclass serum Ab levels on day –1, determined via ELISA. Anti-TNP IgM, IgG1, IgG2c, and IgG2b serum concentrations were determined using anti-TNP IgM, IgG1, IgG2c, and IgG2b standard Abs (Supplemental Figure 2). Symbols represent data from individual animals. Horizontal lines and error bars represent mean + SEM. (C) Anti-OVA IgG2b serum Ab levels on day 13 were determined via ELISA. Bars represent mean + SEM. (D) Difference in footpad thickness between the right and left footpad, determined 3 days after local DTH induction (i.e., day 17). A box-and-whisker diagram with median and sample minimum and maximum is shown. 1 representative of 3 independent experiments is shown. *P < 0.05, **P < 0.01.