Multiple Variables at the Leukocyte Cell Surface Impact Fc γ Receptor-Dependent Mechanisms

Abstract

Fc γ receptors (FcγR) expressed on the surface of human leukocytes bind clusters of immunoglobulin G (IgG) to induce a variety of responses. Many therapeutic antibodies and vaccine-elicited antibodies prevent or treat infectious diseases, cancers and autoimmune disorders by binding FcγRs, thus there is a need to fully define the variables that impact antibody-induced mechanisms to properly evaluate candidate therapies and design new intervention strategies. A multitude of factors influence the IgG-FcγR interaction; one well-described factor is the differential affinity of the six distinct FcγRs for the four human IgG subclasses. However, there are several other recently described factors that may prove more relevant for disease treatment. This review covers recent reports of several aspects found at the leukocyte membrane or outside the cell that contribute to the cell-based response to antibody-coated targets. One major focus is recent reports covering post-translational modification of the FcγRs, including asparagine-linked glycosylation. This review also covers the organization of FcγRs at the cell surface, and properties of the immune complex. Recent technical advances provide high-resolution measurements of these often-overlooked variables in leukocyte function and immune system activation.

Considerations of Antibody Geometric Constraints on NK Cell Antibody Dependent Cellular Cytotoxicity

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IgG-aggregates rapidly up-regulate FcgRI expression at the surface of human neutrophils in a FcgRII-dependent fashion: A crucial role for FcgRI in the generation of reactive oxygen species

“…Results leave the possibility of a role for FcgRIIIa. This point is relevant because FcgRIIIa, like FcgRI, is a classic activating receptor associating with an ITAM-signaling system; it might mediate a number of events previously attributed to FcgRIIIb (39). Alternatively, the balance in expression between the two isoforms may influence cellular responsiveness (39).…”