FCGR2B

FCGR2B Full Name

Fc fragment of IgG, low affinity IIb, receptor (CD32)

FCGR2B Introduction

Fc Fragment of IgG Receptor IIb (FCGR2B), also known as CD32b, is a low-affinity inhibitory receptor for the Fc region of immunoglobulin G (IgG). It belongs to the type II Fcγ receptor family and is the only universally expressed inhibitory FcγR in both humans and mice. Structurally, it is a single-chain transmembrane glycoprotein with extracellular immunoglobulin-like domains. Its key distinguishing feature is an immunoreceptor tyrosine-based inhibitory motif (ITIM) within its cytoplasmic tail. FCGR2B is constitutively and broadly expressed on all B lymphocytes and most innate immune cells, including macrophages, dendritic cells, and mast cells, positioning it as a master regulator of humoral and cellular immune responses.

Figure 1. Strcuture of FCGR2B.

Signaling Mechanism and Molecular Partners
The inhibitory signal is exclusively mediated by its cytoplasmic ITIM motif. Upon co-engagement with an activating receptor, the tyrosine within the ITIM is phosphorylated by Src family kinases. This phosphorylated ITIM then recruits and activates inositol phosphatases, primarily SHIP1 (SH2-containing inositol 5'-phosphatase 1). SHIP1 hydrolyzes the key signaling lipid PIP3 to PIP2, thereby antagonizing the PI3K/Akt survival pathway. It also disrupts the formation of critical signaling complexes, leading to the inhibition of calcium influx, MAPK activation, and NF-κB translocation. This elegantly blocks the downstream signaling cascades initiated by activating receptors.

FCGR2B in Cancer Immunotherapy
In the context of modern oncology, FCGR2B is a double-edged sword. On one hand, its expression on tumor-associated macrophages can limit the efficacy of therapeutic monoclonal antibodies (like rituximab or trastuzumab) by inhibiting the effector cells needed to kill the tumor. On the other hand, FCGR2B can actually enhance the activity of certain agonistic antibodies (immunostimulants) by providing a scaffold for cross-linking. Consequently, FCGR2B has become a major target for drug developers, who are designing antibodies that either block this receptor to unleash the immune system against cancer or utilize it to enhance specific therapies.

Alternate Names for FCGR2B

FCGR2B; Fc fragment of IgG, low affinity IIb, receptor (CD32); CD32; FCG2; CD32B; FCGR2; IGFR2; low affinity immunoglobulin gamma Fc region receptor II-b; CDw32; fcRII-b; Fc gamma RIIb; fc-gamma-RIIb; fc-gamma RII-b; igG Fc receptor II-b; Fc fragment of IgG, low affinity II, receptor for (CD32); Fc fragment of IgG, low affinity IIb, receptor for (CD32);