MALIGNANT TRANSFORMATION OF EARLY LYMPHOID PROGENITORS IN MICE EXPRESSING AN ACTIVATED BLK TYROSINE KINASE

The intracellular signals governing cellular proliferation and develop mental progression during lymphocyte development are incompletely unde rstood. The tyrosine kinase Blk is expressed preferentially in the B l ineage, but its function in B cell development has been largely unexpl ored. We have generated transgenic mice expressing constitutively acti ve Blk [Blk(Y495F)] in the B and T lymphoid compartments. Expression o f Blk(Y495F) in the B lineage at levels similar to that of endogenous Blk induced B lymphoid tumors of limited clonality, whose phenotypes a re characteristic of B cell progenitors at the proB/preB-I to preB-II transition. Expression of constitutively active Blk in the T lineage r esulted in the appearance of clonal, thymic lymphomas composed of inte rmediate single positive cells, Taken together, these results indicate that specific B and T cell progenitor subsets are preferentially susc eptible to transformation by Blk(Y495F) and suggest a role for Blk in the control of proliferation during B cell development.