FcγRIIb on myeloid cells rather than on B cells protects from collagen-induced arthritis.
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.
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
A Seda
AS
Yilmaz-Elis
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
Javier Martin
JM
Ramirez
Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands; and.
Patrick
P
Asmawidjaja
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
Jos
J
van der Kaa
Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands; and.
Anne-Marie
AM
Mus
Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands; and.
Maarten D
MD
Brem
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
Jill W C
JW
Claassens
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
Cor
C
Breukel
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
Conny
C
Brouwers
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Sara M
SM
Mangsbo
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
Peter
P
Boross
Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands; and.
Erik
E
Lubberts
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; j.s.verbeek@lumc.nl.
J Sjef
JS
Verbeek
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002417:Cattle; D002645:Chickens; D024043:Collagen Type II / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D024043:Collagen Type II; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG