Interleukin 21 (IL-21) is a cytokine produced predominantly by cluster of differentiation 4 (CD4+) T-cells and natural killer T-cells. IL-21 is preliminarily expressed in activated cluster of differentiation 4 (CD4+) T-cells and natural killer (NK) T-cells. IL-21 receptor (IL-21R) is a class I cytokine receptor, which requires dimerization with the indispensable common gamma chain (γc) subunit to bind IL-21. IL-21 plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. IL-21 mediates apoptosis in B-CLL cells through up-regulation of the BIM (BH3 family member) and enhances both direct and antibody-dependent cellular cytotoxicity in these cells.