Subversion of the T/B lineage decision in the thymus by lunatic fringe-mediated inhibition of notch-1

Notch-1 signaling is essential for lymphoid progenitors to undergo T cell c ommitment, but the mechanism has not been defined. Here we show that thymoc ytes ectopically expressing Lunatic Fringe, a modifier of Notch-1 signaling , induce lymphoid progenitors to develop into B cells in the thymus. This c ell fate switch resulted from Lunatic Fringe-mediated inhibition of Notch-1 function, as revealed by experiments utilizing lymphoid progenitors in whi ch Notch-1 activity was genetically manipulated. These data identify Lunati c Fringe as a potent regulator of Notch-1 during the T/B lineage decision a nd show that an important function of Notch-1 in T cell commitment is to su ppress B cell development in the thymus.