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Mouse FcγRIIB (CD32B) is the only inhibitory member of the Fc gamma receptor family in mice and is expressed on B cells, macrophages, and dendritic cells (UniProt: P08101). It plays a pivotal role in maintaining peripheral tolerance and preventing autoimmunity by providing a negative feedback loop for B-cell activation and antibody production (PubMed: 15549131). When the receptor binds to IgG-containing immune complexes, its cytoplasmic Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) is phosphorylated, leading to the recruitment of phosphatases that inhibit activating signals (PubMed: 12444137). In mouse models of disease, FcγRIIB deficiency is a hallmark of systemic lupus erythematosus (SLE) susceptibility, highlighting its role in controlling self-reactive B cells. Furthermore, it is a significant target in cancer research, as its expression on tumor cells or the microenvironment can limit the effectiveness of monoclonal antibody therapies by promoting antibody internalization or inhibitory signaling (PubMed: 21131596).
The receptor mediates inhibitory signaling by recruiting the SH2 domain-containing inositol 5-phosphatase (SHIP) to its phosphorylated Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM), which subsequently dephosphorylates key signaling intermediates and suppresses activating signals from receptors like the B-cell receptor (BCR) (PubMed: 10603365).
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