BRUTON TYROSINE KINASE IS TYROSINE-PHOSPHORYLATED AND ACTIVATED IN PRE-B LYMPHOCYTES AND RECEPTOR-LIGATED B-CELLS

The gene encoding Bruton tyrosine kinase (Btk) is known to be mutated in human X chromosome-linked agammaglobulinemia and in the Xid mouse. This kinase was examined in B lymphocytes before and after antigen rec eptor ligation and also in pre-B cells. Btk was found to be catalytica lly activated and tyrosine phosphorylated in response to anti-IgM stim ulation in B cells. This kinase is also constitutively phosphorylated on tyrosine residues in pre-B cells. These findings point to a functio nal role for Btk in pre-antigen and antigen receptor signaling during B-cell development and provide a biochemical explanation for the X-lin ked genetic syndromes already linked to this kinase.