Cutting Edge: The murine high-affinity IgG receptor FcγRIV is sufficient for autoantibody-induced arthritis.
K/BxN serum-induced passive arthritis was reported to depend on the activation of mast cells, triggered by the activating IgG receptor FcγRIIIA, when engaged by IgG1 autoantibodies present in K/BxN serum. This view is challenged by the fact that FcγRIIIA-deficient mice still develop K/BxN arthritis and because FcγRIIIA is the only activating IgG receptor expressed by mast cells. We investigated the contribution of IgG receptors, IgG subclasses, and cells in K/BxN arthritis. We found that the activating IgG2 receptor FcγRIV, expressed only by monocytes/macrophages and neutrophils, was sufficient to induce disease. K/BxN arthritis occurred not only in mast cell-deficient W(sh) mice, but also in mice whose mast cells express no activating IgG receptors. We propose that at least two autoantibody isotypes, IgG1 and IgG2, and two activating IgG receptors, FcγRIIIA and FcγRIV, contribute to K/BxN arthritis, which requires at least two cell types other than mast cells, monocytes/macrophages, and neutrophils.
Département d’Immunologie, Institut Pasteur, Unité d’Allergologie Moléculaire et Cellulaire, F-75015 Paris, France.
David A
DA
Mancardi
Friederike
F
Jönsson
Bruno
B
Iannascoli
Huot
H
Khun
Nico
N
Van Rooijen
Michel
M
Huerre
Marc
M
Daëron
Pierre
P
Bruhns
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000502:physiology*; D001666:Binding Sites, Antibody; D007074:Immunoglobulin G / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D044967:Serum / Q000502:physiology
D001323:Autoantibodies; C517507:FcgammaRIIIA protein, mouse; C522404:Fcgr4 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG