Article
Differential influence of synovial fibroblasts from osteoarthritis vs. rheumatoid arthritis patients on B cell survival and immunoglobulin production
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Published: | September 4, 2017 |
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Background: Rheumatoid Arthritis (RA) is a disease characterized by chronic inflammation of the synovial tissue in joints. It is driven by highly activated B cells. Synovial cells, primarily synovial Fibroblasts (SF) play an important role in activating these B cells. In order to investigate the interactions responsible for B cell activation, a co-culture model was established with RASF and SF from Osteoarthritis (OA) patients.
Methods: IgD+ B cells were isolated from human peripheral blood by MACS and co-cultured w/wo SFs in medium only, in the presence of IFN-gamma or CpG, respectively. B cell subpopulations, survival and proliferation were determined by FACS. IgG and IgM were measured by ELISA.
Results: B cell survival is increased in co-culture after 6 days without additional stimulation (RASF: +20.6% +/-1.2%; OASF: +14.5 % +/- 5.5 %; p=0.02). Proliferation of B cells is already increased after 3 hours of co-culture without additional stimulation (RASF: +13.4 % +/- 2.1 %; OASF: +13.0 % +/- 1.1 %; ns). Addition of CpG leads to an increase of CD38+ B cells without significant differences between RASF and OASF (RASF: 21.3 % +/- 8.6 %; OASF: 16.9 % +/- 6.5 %; ns). After 6 days, an increase in IgM was detected following CpG activation, which was pronounced in the presence of RASF (RASF: from: 6.7 ng/mL +/- 0.9 ng/mL to 517.5 ng/mL +/- 228.4 ng/mL; OASF: from: 5.9 ng/mL +/- 0.3 ng/mL to 189.6 ng/ml +/-204.4 ng/ml; p=0.05). In contrast IgG, induced in the presence of IFN-gamma showed a trend towards an increase OASF co-culture after 12 days (RASF: from: 0.8 ng/mL +/-0.1 ng/mL to 37.8 ng/mL +/-18.5 ng/mL; OASF: from: 0.7 ng/mL +/-0.2 ng/mL to 51.9 ng/mL+/-10.8 ng/mL; p=0.10).
Conclusion: RASF show increased capacity to augment survival of B cells as compared to OASF. In the presence of CpG, B cells produce IgM, with higher levels in the presence of RASF. In contrast, IgG is induced in the presence of IFN-gamma with a trend to increased levels in the presence of OASF. In conclusion, RASF and OASF show different effects on B cells in terms of survival and induction of immunoglobulins.