IgEb immune complexes activate macrophages through FcgammaRIV binding.
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.
Hirano
Masayuki
M
Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Davis
Randall S
RS
Fine
W David
WD
Nakamura
Shugo
S
Shimizu
Kentaro
K
Yagi
Hirokazu
H
Kato
Koichi
K
Stephan
Robert P
RP
Cooper
Max D
MD
D000595:Amino Acid Sequence; D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D045744:Cell Line, Tumor; D006224:Cricetinae; D007073:Immunoglobulin E / Q000502:physiology*; D008262:Macrophage Activation / Q000276:immunology*; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D017452:Receptors, IgG / Q000378:metabolism* / Q000502:physiology; D017386:Sequence Homology, Amino Acid
D000936:Antigen-Antibody Complex; C485700:Fcgr3 protein, mouse; C522404:Fcgr4 protein, mouse; D017452:Receptors, IgG; D007073:Immunoglobulin E