THE PROTEIN DEFECTIVE IN X-LINKED AGAMMAGLOBULINEMIA, BRUTONS TYROSINE KINASE, SHOWS INCREASED AUTOPHOSPHORYLATION ACTIVITY IN-VITRO WHEN ISOLATED FROM CELLS IN WHICH THE B-CELL RECEPTOR HAS BEEN CROSS-LINKED

X-linked agammaglobulinemia is a primary inherited immunodeficiency re sulting in a lack of or dramatic reduction in the number of mature B l ymphocytes and, thus, greatly reduced levels of serum immunoglobulin. The defect results from mutations in the gene for Bruton's tyrosine ki nase (Btk). Using rabbit antisera generated against Btk, we have demon strated an increase in the level of in vitro kinase activity present i n anti-Btk immunoprecipitates from B cells following stimulation with anti-immunoglobulin antibody. This increase in immune complex kinase a ctivity is detectable 1 to 2 min following stimulation and remains ele vated for over 30 min. A similar increase was not seen with two late p re-B cell lines investigated in the same way. This stimulation of acti vity may suggest a role for Btk in signalling through the B cell recep tor or associated proteins, in mature B cells.