CD137 induces proliferation and endomitosis in monocytes.

Peripheral monocytes are short-lived and are replenished from hematopoietic stem cells whose proliferation is believed to be confined to the bone marrow. Human peripheral monocytes are assumed not to be able to proliferate. In this study we show that CD137 (ILA/4-1BB), a member of the tumor necrosis factor receptor family, induces a widespread and profound proliferation of human peripheral monocytes. Macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor are essential, but not sufficient for proliferation. Additional soluble autocrine factors induced by CD137 are required. Induction of proliferation is mediated via reverse signaling through a CD137 ligand, expressed constitutively by peripheral monocytes. The ability of CD137 to induce proliferation in human peripheral monocytes is not shared by any other known molecule.