Neutrophil Activation by Antibody Receptors

Neutrophils, the most abundant leukocytes in blood, are relevant cells of both the innate and the adaptive immune system. Immunoglobulin (Ig) G antibody molecules are crucial activators of neutrophils. IgGs identify many types of pathogens via their two Fab portions and are in turn detected through their Fc portion by specific Fcγ receptors (FcγRs) on the membrane of neutrophils. Thus, antibodies bring the specificity of the adaptive immune response to the potent antimicrobial and inflammatory functions of neutrophils. Two types of FcγRs with several polymorphic variants exist on the human neutrophil. These receptors are considered to be redundant in inducing cell responses. Yet, new evidence presented in recent years on how the particular IgG subclass and the glycosylation pattern of the antibody modulate the IgG–FcγR interaction has suggested that a particular effector function may in fact be activated in response to a specific type of FcγR. In this chapter, we describe the main types of FcγRs on neutrophils and our current view on how particular FcγRs activate various signaling pathways to promote unique effector cell functions, including phagocytosis, activation of integrins, nuclear factor activation, and formation of neutrophil extracellular traps (NETs).