Session Information
Session Title: B cell Biology and Targets in Autoimmune Disease: Rheumatoid Arthritis and Related Diseases
Session Type: Abstract Submissions (ACR)
Background/Purpose
Splenic B cells from collagen-induced arthritis (CIA) mice react to a β2-adrenoceptor (AR) stimulus with increased IL-10 production and adoptive transfer of these cells decreases disease activity. However, B cells from unimmunized mice do not adequately increase IL-10. Therefore, we test the hypothesis that sensitivity to catecholamines changes during CIA. Furthermore, we wanted to test if human peripheral blood B cells from osteoarthritis (OA) and rheumatoid arthritis (RA) patients also increase IL-10 following a β2-adrenergic stimulus.
Methods
FACS to determine AR pathway related proteins (β2-adrenoceptor, G-protein coupled receptor kinase (GRK) 2, phophorylated and unphosphorylated mitogen activated protein kinase p38, and cAMP responsive element binding protein (CREB)) in B cells at different timepoints during CIA. Unstimulated splenic B cells and B cells stimulated with terbutalin, a β2-AR agonist, were used. Human B cells were isolated from peripheral blood of patients with OA or RA and stimulated under different conditions with and without terbutalin. IL-10 protein level was determined by ELISA after 5 days of culture.
Results
In the course of CIA the percentage of β2-AR+ B cells increased and stayed above baseline (ANOVA p<0.05). In contrast, the mean fluorescence intensity (MFI) as measure for the number of receptors per cell remained unchanged. MFI for GRK2 decreased and stayed low from day 6 p.i. (ANOVA p<0.0001). The relative increase in phosphorylation of p38 (ANOVA p<0.001) and CREB (ANOVA p<0.001) following a β2-AR stimulus was augmented starting at day 18 p.i. with a maximum response at day 55 p.i. in the late phase of CIA. In human B cells, similar mechanisms are in place, because β2-AR stimulation of RA, but not OA B cells increased IL-10.
Conclusion
The current data show, that B cells become more sensitive to β2-AR stimuli in the course of CIA, possibly due to a decrease in GRK2 and increase in the percentage of β2-AR expressing splenic B cells. Increased catecholamine sensitivity might support B cell and IL-10 mediated anti-inflammatory mechanisms primarily in the late phase of CIA. A similar mechanism is observed in human peripheral B cells and might be used to improve treatment of autoimmune arthritis.
Disclosure:
G. Pongratz,
None;
C. Wiest,
None;
M. Melzer,
None;
R. Straub,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/%ce%b22-adrenoceptor-signal-is-augmented-in-b-cells-in-the-course-of-arthritis-to-increase-il-10/