CD40 and rheumatoid arthritis: Using polyclonal stimuli (various combinations of cross-linking of BCRs, CD40 engagement, CpG stimulation, and PMA + ionomycin stimulation) to maximize the frequency of cytokine-producing B cells, other groups have found significant decreases in the frequency of IL-10-producing B cells in patients with rheumatoid arthritis [43,44], Graves’ disease [45], and MS [5,23].