Low-affinity immunoglobulin gamma Fc region receptor II (CD32)

CD32, also known as low-affinity immunoglobulin gamma Fc region receptor II, is a family of cell surface receptors that play a pivotal role in modulating immune responses by binding to the Fc region of IgG antibodies [1, 2]. The family comprises three primary isoforms in humans: the activating receptors CD32A (FCGR2A) and CD32C (FCGR2C), and the inhibitory receptor CD32B (FCGR2B) [1, 7]. CD32A is widely expressed on myeloid cells and platelets, where it facilitates phagocytosis and triggers pro-inflammatory cascades upon engagement by immune complexes [11, 15, 17]. Conversely, CD32B is the only inhibitory Fc receptor, serving as a critical negative regulator of B-cell activation and antibody production to maintain immune homeostasis [1, 3, 5]. Therapeutically, CD32 is targeted to either enhance or suppress immune activity depending on the clinical context. CD32B agonists are under development for autoimmune diseases such as systemic lupus erythematosus to dampen B-cell responses, while CD32B antagonists are used in cancer immunotherapy to block inhibitory signals and prevent the internalization of therapeutic antibodies like rituximab from the cell surface [9, 14, 19]. Clinical applications must carefully monitor for safety concerns such as thrombocytopenia and infusion reactions, which can occur due to the activating presence of CD32A on platelets [11, 17]. Genetic polymorphisms in CD32, such as the H131R variant in FCGR2A, serve as important biomarkers that influence the efficacy of monoclonal antibody therapies and individual susceptibility to autoimmune conditions [1, 8, 10].

Other names

FCGR2Fc-gamma RIICD32ACD32BCD32CFcgammaRIILow affinity immunoglobulin gamma Fc region receptor II-aLow affinity immunoglobulin gamma Fc region receptor II-bLow affinity immunoglobulin gamma Fc region receptor II-c

Drugs targeting CD32 primarily modulate its inhibitory or activating signals through different approaches: CD32B agonists recruit inhibitory motifs to suppress autoreactive B-cell and myeloid cell activation in autoimmune disorders [19], while CD32B antagonists (such as BI-1206) block the receptor to prevent antibody internalization, thereby enhancing the residency and efficacy of co-administered monoclonal antibodies and promoting ADCC/ADCP in oncology [9, 14]. Additionally, certain antibodies are Fc-engineered to optimize binding ratios between activating receptors and CD32B to maximize therapeutic index [5], and small molecules like BTK inhibitors can block downstream signaling of CD32A to prevent immune-complex induced platelet activation [15].