Blood Journal
Leading the way in experimental and clinical research in hematology

The high-affinity human IgG receptor FcγRI (CD64) promotes IgG-mediated inflammation, anaphylaxis and anti-tumor immunotherapy

  1. David A. Mancardi1,
  2. Marcello Albanesi2,
  3. Friederike Jönsson3,
  4. Bruno Iannascoli1,
  5. Nico Van Rooijen4,
  6. Xiaoqiang Kang5,
  7. Patrick England6,
  8. Marc Daëron2, and
  9. Pierre Bruhns1,*
  1. 1 Institut Pasteur, Departement d'Immunologie, Laboratoire Anticorps en Therapie et Pathologie, Paris, France;
  2. 2 Institut Pasteur, Departement d'Immunologie, Unite d'Allergologie Moleculaire et Cellulaire, Paris, France;
  3. 3 INSERM, U760, Paris, France;
  4. 4 Department of Molecular Cell Biology, VU Medical Center, Amsterdam, Netherlands;
  5. 5 ImClone Systems, New York, NY, United States;
  6. 6 Institut Pasteur, Proteopole, Plateforme de Biophysique des Macromolecules et de leurs Interactions, Paris, France
  1. * Corresponding author; email: bruhns{at}

Key points

  • Human FcγRI can trigger antibody-induced inflammatory arthritis, thrombocytopenia, airway inflammation and systemic anaphylaxis

  • Human FcγRI can trigger antibody-mediated immunotherapy of mouse metastatic melanoma


IgG receptors (FcγRs) are mandatory for the induction of various IgG-dependent models of autoimmunity, inflammation, anaphylaxis and cancer immunotherapy. A few FcγRs have the ability to bind monomeric IgG, i.e. high-affinity mouse mFcγRI, mFcγRIV and human hFcγRI, whereas all others bind IgG only when aggregated, in complexes or bound to cells or surfaces, i.e. low-affinity mouse mFcγRIIB, mFcγRIII and human hFcγRIIA/B/C and hFcγRIIIA/B. Although it was proposed that high-affinity FcγRs are occupied by circulating IgG, multiple roles for mFcγRI and mFcγRIV have been reported in vivo. The potential roles of hFcγRI that is expressed on monocytes, macrophages and neutrophils, have however not been reported. We therefore investigated the role of hFcγRI in antibody-mediated models of disease and therapy by generating hFcγRI-transgenic mice deficient for multiple endogenous FcRs. hFcγRI was sufficient to trigger autoimmune arthritis and thrombocytopenia, immune complex-induced airway inflammation, active and passive systemic anaphylaxis. We identified monocyte/macrophages to be responsible for thrombocytopenia, neutrophils to be responsible for systemic anaphylaxis, and both cell types to be responsible for arthritis induction. Finally, hFcγRI was capable of mediating antibody-induced immunotherapy of metastatic melanoma. Altogether, our results unravel novel capabilities of human FcγRI that confirm the role of high-affinity IgG receptors in vivo.

  • Submitted July 12, 2012.
  • Accepted December 9, 2012.