Similar to PMA-induced differentiation (21, 196), differentiation via TLR9 signaling induced CLL B-cells to express the PC transcriptional program (e.g., STAT3, IRF4, XBP1s, and BLIMP1) and downregulated expression of B-cell transcriptional programs, including c-MYC, PAX5, BCL6, IRF8, and BACH2 (14, 20, 21). Here, BCL6 is linked to B-cell chronic lymphocytic leukemia.