Figure 3.

Model of FcγR localization and receptor clustering in the cell membrane. Classical monocytes express the activating FcγRIa and FcγRIIa and the inhibitory FcγRIIb with distinct membrane localizations. FcγRIa is predominantly confined to cholesterol-rich lipid raft domains, while FcγRIIa and FcγRIIb are found in non-raft regions in absence of IgG immune complexes (A). Upon IgG immune complex binding FcγRIIa/b are recruited to lipid rafts. Close proximity to each other and to signaling components concentrated at lipid raft domains, enables ITAM/ITIM phosphorylation and induction of intracellular signaling cascades (B). Exclusion of FcγRIIb from lipid rafts due to a mutation in the transmembrane domain causes enhanced activatory signaling (C).