Low affinity immunoglobulin gamma Fc receptor II (CD32) (FcγRII)

The Low affinity immunoglobulin gamma Fc receptor II (CD32) is a critical cell-surface glycoprotein belonging to the immunoglobulin superfamily that mediates cellular responses to IgG-coated particles and immune complexes [1][2]. In humans, this receptor class is divided into three distinct isoforms: the activating receptors FcγRIIa and FcγRIIc, and the inhibitory receptor FcγRIIb [2][3]. FcγRIIa is widely expressed on myeloid cells and platelets, where it triggers phagocytosis and degranulation through its immunoreceptor tyrosine-based activation motif (ITAM) [3]. Conversely, FcγRIIb is the only inhibitory Fc receptor in the human genome, utilizing an immunoreceptor tyrosine-based inhibitory motif (ITIM) to downregulate B-cell activation and inflammatory signaling, making it a pivotal checkpoint in immune homeostasis [4]. Dysregulation or genetic polymorphisms in these receptors are linked to autoimmune diseases such as systemic lupus erythematosus and heparin-induced thrombocytopenia, as well as various B-cell malignancies [4][5]. Pharmacological targeting includes FcγRIIb-specific monoclonal antibodies, such as BI-1206, intended to overcome resistance to rituximab in lymphoma, or obexelimab, designed to suppress B-cell activity in autoimmune conditions [6][7]. Citations: [1] UniProt P12318 (FCGR2A). [2] UniProt P31994 (FCGR2B). [3] Nimmerjahn F, Ravetch JV. Fcgamma receptors as regulators of immune responses. Nat Rev Immunol. 2008;8(1):34-47. [4] Roghanian A, et al. FcγRIIB: A Modulator of Antibody Effector Function and a Target for Cancer Therapy. Cancer Cell. 2015;27(1):15-17. [5] Bolland S, Ravetch JV. Inhibitory pathways: the role of FcγRIIB in autoimmunity and neoplasia. Adv Immunol. 1999;72:149-177. [6] ClinicalTrials.gov Identifier: NCT03571568 (BI-1206). [7] Zenas BioPharma. Obexelimab Product Profile.

Other names

CD32FCGR2Fc gamma receptor IIFCGR2AFCGR2BFCGR2CFc-gamma-RIIaFc-gamma-RIIbFc-gamma-RIIcCD32aCD32bCD32c

FcγRIIb agonism for B-cell inhibition in autoimmune disease; FcγRIIb antagonism to enhance therapeutic antibody efficacy in oncology; FcγRIIa blockade to prevent platelet aggregation or phagocytosis-mediated tissue damage.