Identification of the low affinity receptor for immunoglobulin E on mouse mast cells and macrophages as Fc gamma RII and Fc gamma RIII.
In addition to their well characterized high affinity immunoglobulin E (IgE) receptors (Fc epsilon RI) mast cells have long been suspected to express undefined Fc receptors capable of binding IgE with low affinity. In this paper, we show that Fc gamma RII and Fc gamma RIII, but not Mac-2, on mouse mast cells and macrophages bind IgE-immune complexes. This binding is efficiently competed by 2.4G2, a monoclonal antibody against the extracellular homologous region of both Fc gamma RII and Fc gamma RIII. Furthermore, IgE-immune complexes bind specifically to Fc gamma RII or Fc gamma RIII transfected into COS-7 cells. The association constants of IgE binding estimated from competition experiments are about 3.1 x 10(5) M-1 for Fc gamma RII, and 4.8 x 10(5) M-1 for Fc gamma RIII. Engagement of Fc gamma RII and Fc gamma RIII with IgE-immune complexes (after blocking access to Fc epsilon RI) or with IgG-immune complexes triggers C57.1 mouse mast cells to release serotonin. This release is inhibited by 2.4G2, and at maximum, reaches 30-40% of the intracellular content, about half of the maximal release (60-80%) obtained after Fc epsilon RI engagement. These data demonstrate that mouse Fc gamma RII and Fc gamma RIII are not isotype specific, and that the binding of IgE-immune complexes to these receptors induces cell activation.
Takizawa
F
F
Molecular Allergy and Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852.
Adamczewski
M
M
Kinet
J P
JP
D000818:Animals; D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation / Q000032:analysis*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis* / Q000378:metabolism; D002460:Cell Line; D007073:Immunoglobulin E / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D011961:Receptors, Fc / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D017455:Receptors, IgE; D017452:Receptors, IgG; D012701:Serotonin / Q000378:metabolism; D014162:Transfection
D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG; D012701:Serotonin; D007073:Immunoglobulin E