β2-adrenoceptor signal is augmented in B cells in the course of arthritis to increase IL-10

Abstract

Splenic B cells from collagen-induced arthritis (CIA) mice react to a β 2-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 and investigate if human blood B cells from osteoarthritis (OA) and rheumatoid arthritis (RA) patients also increase IL-10 following a β 2-adrenergic stimulus. In the course of CIA the percentage of β 2-AR+ B cells increased (ANOVA p 0.05 ), as determined by FACS. Mean fluorescence intensity (MFI) for G-protein coupled receptor kinase (GRK2) decreased from day 6 p.i. (ANOVA p 0.0001 ). The relative increase in phosphorylation of p38 (ANOVA p 0.001 ) and cAMP responsive element binding protein (CREB, ANOVA p 0.001 ) following a β 2-AR stimulus is augmented in late CIA. In human B cells, similar mechanisms are in place, because β 2-AR stimulation of RA but not OA B cells increased IL-10, as determined by ELISA. In conclusion, B cells become more sensitive to β 2-AR stimuli in the course of CIA, possibly due to decreased GRK2 and increased percentage of β 2AR+ B cells. Increased catecholamine sensitivity might support B cell and IL-10 mediated anti-inflammatory mechanisms in late CIA. A similar mechanism is observed in human B cells and might be used to improve treatment of autoimmune arthritis.