B-cell chronic lymphocytic leukemia (CLL), the most prevalent leukemia in Western societies, is characterized by the progressive accumulation of CD5+ malignant B lymphocytes within the blood, the bone marrow (BM) and the lymph nodes (LNs).While the circulating CLL pool is mainly cell cycle arrested and resistant to apoptosis, the proliferative compartment likely resides within proliferation centers that are mainly found in LNs and to a lesser extent in BM.A complex interplay of malignant and accessory cells such as stromal cells but also certain Tf cell subsets, the extracellular matrix, and soluble factors within these zones determines the balance between proliferating and resting cells.