SAT0043 Impaired B cell immunity in IL-27R knock-out mice in collagen induced arthritis. (23rd January 2014)

• Record Type: Journal Article
• Authors: Corneth, O.B.J.; Mus, A.-M.C.; Asmawidjaja, P.S.; Kil, L.; Hendriks, R.W.; Lubberts, E.
• Is Part Of: Annals of the rheumatic diseases. Volume 71(2012)Supplement 3
• Page Start: 485
• Page End: 485
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-eular.2991
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Collagen induced arthritis (CIA), a mouse model for rheumatoid arthritis, is both B cell and T helper (Th) 17 cell mediated. Interleukin 27 receptor (IL27R) signaling upregulates IL12 receptor expression on naïve T cells and inhibits Th17 differentiation. In addition, IL27R expression is upregulated on activated B cells. However, the role of IL27R signaling on B cells is not fully understood. We therefore aim to investigate the role of IL27R signaling in B cell immunity and the pathogenesis of CIA. Objectives: To investigate the role of IL27R signalling on B cells in CIA. Methods: For CIA, mice were immunized with complete Freund's adjuvant and chicken collagen type II (CFA/CII) and boosted 21 days later. For AIA, mice were immunized with CFA and methylated bovine serum albumin (mBSA) and 7 days later a stimulus with mBSA was given directly in the knee joint. For B cell activation experiments, mice were immunized with DNP-Ficoll and sacrificed 7 days later. Results: IL27R knockout mice showed a decreased CIA arthritis score compared to wild type controls. Analysis of B cells in CIA by immunohistochemistry and flow cytometry showed severely decreased germinal center formation in IL27R knockout mice. In addition, plasma cell formation and auto-antibody formation were decreased compared to controls, suggesting an intrinsic defect in B cell differentiation upon activation. To exclude that the phenotype of IL27R knockout mice in CIA was caused by a defect in Th17 pathogenicity, we made use of the Th17 mediated antigen induced arthritis (AIA) model, which is B cell independent. IL27R knockout animals developed comparable arthritis to controls. Based on these data we concluded that T cells respond normally in these mice. We therefore further analyzed B cell responses using the T cell independent DNP-Ficoll immunization model. IL27R knockout mice showed lower IgM and IgG3 plasma cell counts in spleen and lower DNP specific IgM and IgG3 antibody levels in serum. These data further support impaired B cell differentiation after activation. Conclusions: Here we show that IL27R knockout mice are protected against full blown CIA. Th17 cells in these mice are functionally normal. However, terminal B cell differentiation appears to be impaired, suggesting a critical role for IL27R signaling in B cell immunity. Disclosure of Interest: None Declared