Several types of FcR have been discovered, including FcγRI, FcγRIIa/IIb/IIc, and FcγIIIa/IIIb. FcγRIIIa and FcγRIIa are activating receptors due to the presence of an immunoreceptor tyrosine-based activation motif either in the accessory signaling γ chain (FcγRIIIa) or cytoplasmic domain (FcγRIIa). FcγRIIIa is expressed on macrophages, natural killer (NK) cells, and some dendritic cells, while FcγRIIa is expressed on macrophages, neutrophils, dendritic cells, and some mast cells. Previous studies that have examined single nucleotide polymorphisms (SNPs) of Fc receptor (FcR) genes demonstrated that FCGR3A gene SNPs are associated with response to rituximab in patients with FL.7 This is in contrast to patients with chronic lymphocytic leukemia, and these differences in response to rituximab are correlated with binding affinity of FcR with ADCC effector cells, suggesting a more important role of ADCC in lymphoma. It is known that the FCGR3A of valine (V) allele has a higher affinity to human immunoglobulin G (IgG) than the phenylalanine (F) allele, and that cells bearing the FCGR3A V allele mediate ADCC more effectively.
Kim D H, et al. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma[J]. Blood, 2006, 108(8): 2720-2725.