Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcγRIIB and dectin-1

Nat Med. 2012 Sep;18(9):1401-6. doi: 10.1038/nm.2862.


Complement is an ancient danger-sensing system that contributes to host defense, immune surveillance and homeostasis. C5a and its G protein–coupled receptor mediate many of the proinflammatory properties of complement. Despite the key role of C5a in allergic asthma, autoimmune arthritis, sepsis and cancer, knowledge about its regulation is limited. Here we demonstrate that IgG1 immune complexes (ICs), the inhibitory IgG receptor FcγRIIB and the C-type lectin–like receptor dectin-1 suppress C5a receptor (C5aR) functions. IgG1 ICs promote the association of FcγRIIB with dectin-1, resulting in phosphorylation of Src homology 2 domain–containing inositol phosphatase (SHIP) downstream of FcγRIIB and spleen tyrosine kinase downstream of dectin-1. This pathway blocks C5aR-mediated ERK1/2 phosphorylation, C5a effector functions in vitro and C5a-dependent inflammatory responses in vivo, including peritonitis and skin blisters in experimental epidermolysis bullosa acquisita. Notably, high galactosylation of IgG N-glycans is crucial for this inhibitory property of IgG1 ICs, as it promotes the association between FcγRIIB and dectin-1. Thus, galactosylated IgG1 and FcγRIIB exert anti-inflammatory properties beyond their impact on activating FcγRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antibodies, Monoclonal
  • Autoimmune Diseases / immunology*
  • Blotting, Western
  • Calcium / metabolism
  • Cell Adhesion / immunology
  • Complement C5a / administration & dosage
  • Complement C5a / immunology*
  • Female
  • Immunoglobulin G / immunology*
  • Inositol Polyphosphate 5-Phosphatases
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement / metabolism*
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism*
  • Surface Plasmon Resonance
  • Syk Kinase


  • Antibodies, Monoclonal
  • C5AR1 protein, human
  • Immunoglobulin G
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Receptors, IgG
  • dectin 1
  • Complement C5a
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse
  • Phosphoric Monoester Hydrolases
  • Inositol Polyphosphate 5-Phosphatases
  • Calcium