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.
© 2012 New York Academy of Sciences.