Article abstract
Nature Immunology 8, 762 - 771 (2007)
Published online: 10 June 2007 | doi:10.1038/ni1477
IgEb immune complexes activate macrophages through Fc
RIV binding
Masayuki Hirano1,2,3, Randall S Davis1,2,4,5,6, W David Fine1,3, Shugo Nakamura7, Kentaro Shimizu7, Hirokazu Yagi8, Koichi Kato8, Robert P Stephan1,2 & Max D Cooper1,2,3,6,9
Abstract
Because functional analysis of Fc receptors (FcRs) relies heavily on mouse models, the identification of another Fc
receptor is particularly noteworthy. We demonstrate that FcRIV, identified here as the mouse ortholog of primate FcRIII, required association of the FcR -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, FcRIV 'preferentially' bound immunoglobulin E antibodies of the 'b' allotype (IgEb) as well as IgG2a and IgG2b antibodies. Ligation of FcRIV by antigen-IgEb immune complexes promoted macrophage-mediated phagocytosis, presentation of antigen to T cells, production of proinflammatory cytokines and the late phase of cutaneous allergic reactions. IgEb antibody–mediated modification of macrophage responses may therefore influence mouse asthma models and strain-dependent differences in parasite susceptibility.
- Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
- Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
- Departments of Pediatrics and Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Correspondence to: Max D Cooper1,2,3,6,9 e-mail: max.cooper@ccc.uab.edu
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