Glatiramer Acetate Stimulates Regulatory B Cell Functions

The control of the activities of regulatory B (Breg) cells in immune disorders is an emerging therapeutic strategy for the recovery of immune homeostasis. Manipulating B cells using numerous drugs in vivo affect their regulatory functions, although a direct link has not yet been demonstrated. Glatiramer acetate (GA) is a synthetic polypeptide that is used in the treatment of inflammatory and autoimmune diseases. We experimented on an in vitro coculture system to determine its direct effects on the Breg cell properties of human B cells. We found that GA improves the B cell dependent control of T cells' immune responses. When B cells are stimulated by GA, the T cell proliferation and their Thl IFN-gamma production are further inhibited, whereas the B cell production of IL-10 is further enhanced. GA binds preferentially to the memory B cells and the activation of sorted B cell subsets shows that GA-dependent increased Breg cell activities are specifically supported by the B cells' memory compartment. Moreover, we found that the defective regulations that emerge from the B cells of systemic lupus erythematosus patients can be restored by GA stimulation. Overall, these data demonstrate that GA stimulates the Breg functions mainly by shifting the memory B cells known to contribute to the T cell dependent inflammatory response into Breg cells. Our results also indicate that GA treatment could be a useful therapy for recovering the Breg cells in autoimmune situations in which their activities are defective.