Hypothetical model of immune regulation in CLL. Circulating CLL cells are anergic B cells with low surface IgM levels after exposure to (super)antigen. (1) CLL cells express several molecules that may have regulatory activity on plasma cells either by cell contact (eg, FasL, CD27, and/or or PDL1) or by deprivation of soluble factors essential for plasma cell survival (eg, BCMA, refer to text and Table 1).^72,73  (2) Upon activation in tissue, CLL cells differentiate into B10 cells to produce immunosuppressive IL-10 and upregulate molecules with regulatory activity on other effector arms of the immune system. (3) Among the targets of IL-10, monocytes/macrophages are suppressed in their activity to produce tumor necrosis factor-α.