CD32 Activators

CD32, also known as Fc gamma receptor II (FcγRII), is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. It is primarily expressed on various immune cells, including B cells, monocytes, macrophages, and dendritic cells. CD32 plays a crucial role in regulating immune responses by binding to the Fc portion of immunoglobulins, particularly IgG antibodies, and mediating downstream signaling events. Its function is diverse and context-dependent, contributing to both immune activation and immune regulation. Upon ligand binding, CD32 can elicit various cellular responses, including phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), cytokine production, and modulation of immune cell activation thresholds. Additionally, CD32 is involved in immune complex clearance and antigen presentation, thereby influencing both innate and adaptive immune responses.

The activation of CD32 is mediated through the engagement of its extracellular domain with the Fc portion of IgG antibodies. This interaction triggers intracellular signaling cascades via its cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs) or immunoreceptor tyrosine-based inhibitory motifs (ITIMs), depending on the isoform and cell type. For activating isoforms, such as CD32A and CD32C, ITAMs recruit protein tyrosine kinases such as Lyn, Syk, and Fyn upon receptor clustering, leading to phosphorylation events that propagate downstream signaling pathways involved in immune cell activation. Conversely, inhibitory isoforms, such as CD32B, contain ITIMs that recruit protein tyrosine phosphatases upon ligand binding, resulting in the inhibition of immune cell activation and attenuation of inflammatory responses. Thus, the activation of CD32 is tightly regulated and influences immune cell behavior and function in both health and disease contexts.