title: 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: Laboratory of Tolerance and Autoimmunity, German Rheumatism Research Center, Berlin, Germany.
authors: Constanze
authors: C
authors: Hess
authors: André
authors: A
authors: Winkler
authors: Alexandra K
authors: AK
authors: Lorenz
authors: Vivien
authors: V
authors: Holecska
authors: Véronique
authors: V
authors: Blanchard
authors: Susanne
authors: S
authors: Eiglmeier
authors: Anna-Lena
authors: AL
authors: Schoen
authors: Josephine
authors: J
authors: Bitterling
authors: Alexander D
authors: AD
authors: Stoehr
authors: Dominique
authors: D
authors: Petzold
authors: Tim
authors: T
authors: Schommartz
authors: Maria M M
authors: MM
authors: Mertes
authors: Carolin T
authors: CT
authors: Schoen
authors: Ben
authors: B
authors: Tiburzy
authors: Anne
authors: A
authors: Herrmann
authors: Jörg
authors: J
authors: Köhl
authors: Rudolf A
authors: RA
authors: Manz
authors: Michael P
authors: MP
authors: Madaio
authors: Markus
authors: M
authors: Berger
authors: Hedda
authors: H
authors: Wardemann
authors: Marc
authors: M
authors: Ehlers
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D025461:Feedback, Physiological; D005260:Female; D006031:Glycosylation; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D012794:Sialic Acids / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D012794:Sialic Acids
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