MilliporeSigma

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
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
IgG3, Kappa from human myeloma plasma, purified immunoglobulin, >90% (microfluidic capillary gel electrophoresis)
Sigma-Aldrich
IgG2, Kappa from human myeloma plasma, purified immunoglobulin, >95% (SDS-PAGE)
Sigma-Aldrich
Anti-FcεRI Antibody, γ subunit, Upstate®, from rabbit
Sigma-Aldrich
IgG3, Kappa from murine myeloma, clone DX, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
IgM from bovine serum, reagent grade, ≥95% (SDS-PAGE or HPLC), buffered aqueous solution