EXPRESSION OF BRUTONS TYROSINE KINASE PROTEIN WITHIN THE B-CELL LINEAGE

Defects in the gene encoding Bruton's tyrosine kinase (Btk), normally expressed in B cells, cause X-linked agammaglobulinemia (XLA). The phe notype of XLA is characterized by a lack of circulating B cells and im munoglobulin. It has been suggested that B cell maturation from the pr e-B cell stage to more mature stages is dependent on the appropriate e xpression of this gene. The Btk mRNA is expressed in B cells and myelo id cells, but protein expression in relation to B cell maturation has not been determined. Moreover, expression of the Btk protein has so fa r only been investigated in human Epstein-Barr virus-transformed B cel l lines, and in murine splenocytes and B cell lines. We have developed an antiserum which recognizes the human Btk protein and shown that no rmal human tonsillar B cells, peripheral blood monocytes and myeloid c ells express the protein, whereas tonsil-derived T cells do not. We al so show that the protein is present in early and mature human B cell l ines, but is absent in terminally differentiated plasma cell lines. Fu rthermore, expression is reduced or absent in three B lineage cell lin es derived from two patients with defined genetic mutations in Btk and suffering from XLA.