Adenosine receptor 2a agonists target mouse CD11c+T-bet+ B cells in infection and autoimmunity

CD11c(+)T-bet(+) B cells are recognized as an important component of humoral immunity and autoimmunity. These cells can be distinguished from other B cells by their higher expression of the adenosine receptor 2a. Here we address whether A(2A) receptor activation can affect CD11c(+)T-bet(+) B cells. We show that administration of the A(2A) receptor agonist CGS-21680 depletes established CD11c(+)T-bet(+) B cells in ehrlichial-infected mice, in a B cell-intrinsic manner. Agonist treatment similarly depletes CD11c(+)T-bet(+) B cells and CD138(+) B cells and reduces anti-nuclear antibodies in lupus-prone mice. Agonist treatment is also associated with reduced kidney pathology and lymphadenopathy. Moreover, A(2A) receptor stimulation depletes pathogenic lymphocytes and ameliorates disease even after disease onset, highlighting the therapeutic potential of this treatment. This study suggests that targeting the adenosine signaling pathway may provide a method for the treatment of lupus and other autoimmune diseases mediated by T-bet(+) B cells. CD11c(+)T-bet(+) B cells have been linked with different autoimmune diseases, but targeting these cells has been challenging. Here the authors use an adenosine 2A receptor agonist to deplete these B cells and to inhibit or reverse autoimmune symptoms and pathology in mice.