IgEb immune complexes activate macrophages through FcgammaRIV binding.

Nature immunology (2007-06-15)
Masayuki Hirano, Randall S Davis, W David Fine, Shugo Nakamura, Kentaro Shimizu, Hirokazu Yagi, Koichi Kato, Robert P Stephan, Max D Cooper

Because functional analysis of Fc receptors (FcRs) relies heavily on mouse models, the identification of another Fcgamma receptor is particularly noteworthy. We demonstrate that FcgammaRIV, identified here as the mouse ortholog of primate FcgammaRIII, required association of the FcR gamma-chain for optimal expression and function on myeloid cells; its signaling potential was also enhanced by a cytoplasmic 'YEEP' motif that was able to recruit the adaptor molecule Crk-L and phosphatidylinositol-3-OH kinase. Unexpectedly, FcgammaRIV 'preferentially' bound immunoglobulin E antibodies of the 'b' allotype (IgE(b)) as well as IgG2a and IgG2b antibodies. Ligation of FcgammaRIV by antigen-IgE(b) immune complexes promoted macrophage-mediated phagocytosis, presentation of antigen to T cells, production of proinflammatory cytokines and the late phase of cutaneous allergic reactions. IgE(b) antibody-mediated modification of macrophage responses may therefore influence mouse asthma models and strain-dependent differences in parasite susceptibility.

Product Number
Product Description

IgG2, Kappa from human myeloma plasma, purified immunoglobulin, >95% (SDS-PAGE)
IgG3, Kappa from human myeloma plasma, purified immunoglobulin, >90% (microfluidic capillary gel electrophoresis)
IgM from bovine serum, reagent grade, ≥95% (SDS-PAGE or HPLC), buffered aqueous solution
IgG3, Kappa from murine myeloma, clone DX, purified immunoglobulin, buffered aqueous solution