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CD40, a member of the tumor necrosis factor (TNF) receptor family that is expressed on B cells, monocytes, dendritic cells, endothelial cells, and epithelial cells, as well as on B cell lymphomas and carcinomas, activates multiple signaling pathways. In B cells, the response to CD40 is complex and depends on the maturation status of the cell. It is well established that CD40 can promote cell survival through up-regulation of the expression of genes encoding antiapoptotic proteins. However, a new role for CD40 signaling is being recognized in promoting progression through the cell cycle. The roles of the phosphoinositide 3-kinase, mitogen-activated protein kinase, and nuclear factor κB pathways in mediating CD40 stimulation of the cell cycle are described.