Expression of CD137 ligand on murine bone marrow cells has been documented at the mRNA level, and CD137 ligand signaling takes place not only in differentiated hematopoietic cells but also in bone marrow cells. Proliferation of murine bone marrow cells treated with M-CSF is enhanced when the cells are exposed to immobilized CD137 protein. CD137 ligand signals also inhibit receptor activator of nuclear factor-^B (RANK) ligand-induced differentiation of bone marrow cells towards osteoclasts (Saito et al., 2004). As mentioned above, a missing differentiation signal may also be the cause for the amplification of
Costimulation of primary antibody response s^CD40 ligand c=c CD40 ra»"vCD137 >-c:> CD137 ligand
Figure 3.2. Depiction of the suggested roles of the CD40 and CD137 receptor/ligand systems in B cell maturation and the costimulation of humoral immune responses. At the first antigen encounter the CD40 receptor/ligand system costimulates B cell proliferation and immunoglobulin class switch. At the second antigen encounter during affinity maturation the CD137 receptor/ligand system costimulate B cell proliferation and immunoglobulin synthesis. FDC: follicular dendritic cell.
myeloid progenitors in CD137 ligand-deficient mice (Kwon et al., 2002). Taken together, these data suggest that the CD137 ligand signal directs differentiation of bone marrow cells away from osteoclast and into the myeloid lineage. And the CD137 ligand signal remains important even after differentiation of the bone marrow cells to monocytes and macrophages, as CD137 ligand provides activating and growth-enhancing signals to these cells.
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