IgG-effector functions: "the good, the bad and the ugly"

IgG-antibodies are potent and versatile mediators of host protection. They elicit their biological effects through specific interaction of the Fc-part with complement, specific cellular receptors, or both. Several factors should be taken into consideration when analyzing the nature and intensity of the immunological response elicited via IgG-effector functions, especially for the family of IgG-Fc receptors (FcγRs) exclusively expressed on immune cells. These include the various classes of leukocyte FcγR, expressed variably on different immune cells, each with distinct affinity for every IgG subclass, as well as genetic FcγR-polymorphisms affecting expression and affinity for IgG. Furthermore, various aspects of the IgG itself are also crucial for the outcome of the biological response. These include endogenously encoded IgG-polymorphisms, such as IgG3 polymorphisms, and post-transcriptional IgG-modifications, in particular IgG-Fc-glycosylation, affecting IgG effector functions through modified binding affinity to FcγR. These latter aspects concerning the variability in IgG3 on its half-life and placental transport and the clinical consequences of altered IgG-quality through glycosylation, will be the focus of this review.