In addition to antigen stimulation, B-CLL cells also receive receptor-mediated signals as well as soluble factors, such as cytokines and chemokines, from other lymphoid and nonlymphoid cells. In particular, it is thought that in vivo B-CLL cell interactions with stromal cells and "nurselike" cells can rescue normally (ex vivo) apoptosis-prone B-CLL cells from death. The natural ligand of CD38, CD31, is displayed on stromal and nurselike cells as well as on endothelial cells and might be involved in setting up these rescue signals. Such contact derived and soluble signals can go on to up-regulate anti-apoptotic genes, such as Bcl-2, survivin, and Mcl-1, which could rescue B-CLL cells from apoptosis and fascilitate their growth.
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