Abstract: Provided are methods for manipulating aspects of lymphopoiesis by modulating and controlling Notch signaling, thereby providing treatment for diseases of the immune system. Accordingly, there are provided methods for selectively modulating T cell fate commitment of a common lymphoid progenitor at the expense of B cell fate commitment, and in the converse for selectively modulating B cell fate commitment of a common lymphoid progenitor at the expense of T cell fate commitment. Also provided are methods for treating patients suffering from a disease or disorder of T cell origin, or conversely of B cell origin. Further provided are methods for selectively killing B cells in a committed population of B cells, such as in a patient suffering from B cell leukemia or lymphoma; as well as methods for selectively killing T cells in a committed population of T cells such as in a patient suffering from diseases of T cell origin.