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FcγRIIb on myeloid cells rather than on B cells protects from collagen-induced arthritis
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2014 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 192, no 12, 5540-5547 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2014. Vol. 192, no 12, 5540-5547 p.
National Category
Immunology in the medical area
URN: urn:nbn:se:uu:diva-245260DOI: 10.4049/jimmunol.1303272PubMedID: 24842758OAI: oai:DiVA.org:uu-245260DiVA: diva2:790972
Available from: 2015-02-26 Created: 2015-02-26 Last updated: 2015-04-17Bibliographically approved

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Mangsbo, Sara M
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