Chronic Lymphocytic Leukemia (CLL) is the most common adult leukemia in western society. Currently, there is no curative treatment for CLL and the disease is associated with concomitant immunosuppression, which potentially interferes with therapy. We have discovered a novel immunosuppressive molecule, CD200, and have shown it to be over-expressed in CLL cells and in the serum of CLL patients (sCD200). We hypothesized that this may represent a target for new therapeutics. We propose to document that sCD200 in CLL serum is immunosuppressive and explore the source of sCD200. We are developing a mouse model allowing for the first time growth of human CLL in mice, which will then be used: (i) to explore the ability of a panel of anti-human CD200 antibodies to inhibit growth of CLL, and (ii) to characterize whether anti-CD200 directed synthetic small chemicals can be used as novel therapeutics for CLL.