title: Novel roles for the IgG Fc glycan.
abstract: IgG antibodies trigger leukocyte activation and inflammation by forming immune complexes that crosslink activating Fcγ receptors (FcγRs). This is essential to combat infection, but detrimental if antibodies target or cross-react with autoantigens. The high specificity and long serum half-life of IgG antibodies confers tremendous therapeutic potential. Indeed, antibodies have been successfully employed to target cancers, autoreactive B cells, and pro-inflammatory cytokines. Conversely, IgG antibodies can also initiate anti-inflammatory responses. In the form of intravenous immunoglobulin (IVIG), IgGs are routinely administered to treat inflammatory autoimmune diseases. Importantly, the N-linked glycans on the IgG Fc are absolutely required for initiating these IgG effector functions. In fact, the Fc glycan composition dictates IgG affinity to individual FcγRs, and in a broader sense, binding to different FcγRs classes: activating, inhibitory, and anti-inflammatory (dendritic cell-specific ICAM-3 grabbing nonintegrin, DC-SIGN). The Fc glycan requirements to initiate and suppress inflammation will be discussed herein.
authors.affiliation: Leonard Wagner Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10065, USA. ranthony01@rockefeller.edu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Anthony
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wermeling
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Ravetch
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry* / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000737:chemistry / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D051379:Mice; D018448:Models, Immunological; D008958:Models, Molecular; D015394:Molecular Structure; D011134:Polysaccharides / Q000737:chemistry* / Q000276:immunology*
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D011134:Polysaccharides