FcγRIIb on Myeloid Cells Rather than on B Cells Protects from Collagen-Induced Arthritis

  • Yilmaz-Elis A
  • Ramirez J
  • Asmawidjaja P
  • et al.
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Abstract

Extensive analysis of a variety of arthritis models in germline KO mice has revealed that all four receptors for the Fc part of IgG (FcγR) play a role in the disease process. However, their precise cell type–specific contribution is still unclear. In this study, we analyzed the specific role of the inhibiting FcγRIIb on B lymphocytes (using CD19Cre mice) and in the myeloid cell compartment (using C/EBPαCre mice) in the development of arthritis induced by immunization with either bovine or chicken collagen type II. Despite their comparable anti-mouse collagen autoantibody titers, full FcγRIIb knockout (KO), but not B cell–specific FcγRIIb KO, mice showed a significantly increased incidence and severity of disease compared with wild-type control mice when immunized with bovine collagen. When immunized with chicken collagen, disease incidence was significantly increased in pan-myeloid and full FcγRIIb KO mice, but not in B cell–specific KO mice, whereas disease severity was only significantly increased in full FcγRIIb KO mice compared with incidence and severity in wild-type control mice. We conclude that, although anti-mouse collagen autoantibodies are a prerequisite for the development of collagen-induced arthritis, their presence is insufficient for disease development. FcγRIIb on myeloid effector cells, as a modulator of the threshold for downstream Ab effector pathways, plays a dominant role in the susceptibility to collagen-induced arthritis, whereas FcγRIIb on B cells, as a regulator of Ab production, has a minor effect on disease susceptibility.

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APA

Yilmaz-Elis, A. S., Ramirez, J. M., Asmawidjaja, P., van der Kaa, J., Mus, A.-M., Brem, M. D., … Verbeek, J. S. (2014). FcγRIIb on Myeloid Cells Rather than on B Cells Protects from Collagen-Induced Arthritis. The Journal of Immunology, 192(12), 5540–5547. https://doi.org/10.4049/jimmunol.1303272

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