As previously shown, the sympathetic nervous system (SNS) shows proinfl ammatory activity during initiation of arthritis but is anti-infl ammatory in established collagen-induced arthritis (CIA). Interleukin 10 (IL-10)-producing B cells suppress arthritis and are a potential target of the SNS because (1) B cells express functional β 2 -adrenoceptors (β 2 ARs) and (2) IL-10, at least in monocytes/macrophages, is regulated in a cAMP/ PKA/CREB-dependent manner. Objective To test the hypothesis

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... anti-infl ammatory effects of the SNS in CIA are mediated by stimulating IL-10-producing anti-infl ammatory B cells. Methods Collagen-induced arthritis in DBA/1 mice, sympathectomy, adoptive B cell transfer, in vitro B cell culture, and assessment of B cell IL-10 production. Results and conclusion Mice treated with B cells from SNS-intact mice showed less severe arthritis than mice treated with B cells from sympathectomised mice. This anti-infl ammatory action of B cells from SNS-intact mice correlated with increased IL-10 produced by B cells, which was mediated by norepinephrine (NE), in a β 2 AR, PKA-dependent manner. However, an NE-mediated increase in IL-10 was seen only in B cells from immunised but not naive mice, explaining in part the antiinfl ammatory properties of the SNS in the late phase of arthritis. Finally, animals treated with B cells isolated from immunised mice and activated in vitro in the presence of a β 2 AR stimulus showed a decrease in arthritis severity in comparison with controls, an approach that might be used for future cellular treatment strategies. MATERIAL AND METHODS Animals, induction of arthritis and arthritis scoring Male DBA/1 mice 6-8 weeks old (Elevage Janvier, Le Genest St Isle, France) were housed in cages and