Fc receptors: Cell activators of antibody functions

Abstract

At the onset of an infection early defense systems, such as complement, get into action. Specialized leu-kocytes (white blood cells) of the innate immune sys-tem, including monocytes, macrophages, and neutro-phils also participate as a first line of defense against infections. These early responses are rapid but not very specific and are usually not enough to clear com-pletely many infections. The adaptive immune system is also needed to finish the job against many micro-organisms. Antibody molecules, produced during the adaptive immune response, are crucial for preventing recurrent infections. Although, IgG antibodies are essential for controlling infections, these molecules do not directly damage the microorganisms they recog-nize. Today, it is established that leukocytes of the innate immune system are responsible for the protec-tive effects of these antibodies. IgG molecules bind to their cognate antigens and are in turn recognized by specific receptors (Fcγ receptors) on the membrane of leukocytes. Crosslinking these receptors on the sur-face of leukocytes leads to activation of several effec-tor cell functions. These effector functions are geared toward the destruction of microbial pathogens and the induction of an inflammatory state that is benefi-cial during infections. However, in autoimmune dis-eases, antibodies can direct these effector functions against normal tissues and cause severe tissue damage. In recent years, several factors that can modulate the IgG-FcγR interaction have been elucidated. In this review, we describe the main types of Fcγ receptors, and our current view of how antibody variants inter-act with these receptors to initiate different cell re-sponses. In addition, new findings on the signaling role of individual Fcγ receptors are also discussed.