Cell cycle arrest and apoptosis induced by Notch1 in B cells

Notch receptors play various roles for cell fate decisions in developing or gans, although their functions at the cell level are poorly understood. Rec ently, we found that Notch1 and its ligand are each expressed in juxta-pose d cell compartments in the follicles of the bursa of Fabricius, the central organ for chicken B cell development. To examine the function of Notch1 in B cells, a constitutively active form of chicken Notch1 was expressed in a chicken B cell line, DT40, by a Cre/loxP-mediated inducible expression sys tem. Remarkably, the active Notch1 caused growth suppression of the cells, accompanied by a cell cycle inhibition at the G(1) phase and apoptosis. The expression of Hairy1, a gene product up-regulated by the Notch1 signaling, also induced the apoptosis, but no cell cycle inhibition. Thus, Notch1 sig naling induces apoptosis of the B cells through Hairy1, and the G(1) cell c ycle arrest through other pathways. This novel function of Notch1 may accou nt for the recent observations indicating the selective inhibition of early B cell development in mice by Notch1.