Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation.
Immunoglobulin G (IgG) mediates pro- and anti-inflammatory activities through the engagement of its Fc fragment (Fc) with distinct Fcg receptors (FcgRs). One class of Fc-FcgR interactions generates pro-inflammatory effects of immune complexes and cytotoxic antibodies. In contrast, therapeutic intravenous gamma globulin and its Fc fragments are anti-inflammatory. We show here that these distinct properties of the IgG Fc result from differential sialylation of the Fc core polysaccharide. IgG acquires anti-inflammatory properties upon Fc sialylation, which is reduced upon the induction of an antigen-specific immune response. This differential sialylation may provide a switch from innate anti-inflammatory activity in the steady state to generating adaptive pro-inflammatory effects upon antigenic challenge.
Kaneko
Yoshikatsu
Y
Laboratory of Molecular Genetics and Immunology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Nimmerjahn
Falk
F
Ravetch
Jeffrey V
JV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D001168:Arthritis / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000628:therapy; D006031:Glycosylation; D006207:Half-Life; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009393:Nephritis / Q000276:immunology; D011134:Polysaccharides; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D012794:Sialic Acids / Q000032:analysis*
D000911:Antibodies, Monoclonal; C499172:Fcgr2b protein, mouse; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D011134:Polysaccharides; D011961:Receptors, Fc; D017452:Receptors, IgG; D012794:Sialic Acids