EXPRESSION OF BRUTON TYROSINE KINASE IN B-LYMPHOBLASTOID CELL-LINES FROM X-LINKED AGAMMAGLOBULINEMIA PATIENTS

X-linked agammaglobulinaemia (XLA) is an immunodeficiency caused by mu tations in Bruton's tyrosine kinase (Btk) and is characterized by ail almost complete arrest of B cell development. We analysed expression o f Btk in B lymphoblastoid cell lines (BLCL) derived from four unrelate d XLA patients. In one patient, with a 3.5 kb genomic deletion encompa ssing the first (untranslated) exon, mRNA levels and in vitro kinase a ctivities were very low. The patient manifested a mild phenotype with a delayed onset of the disease. Another mutation: in which the intron 3 donor splice site is lost, was also associated with very low mRNA le vels and an absence of detectable Btk protein. Patients with this muta tion showed extensive heterogeneity of the immunological phenotype. In the BLCL of a third patient, with an Arg(288) substitution in the SH2 domain, the mutation did not appear to affect the expression level, n or to abrogate in vitro phosphorylation activity. In the BLCL of the f ourth patient, with an Arg(28) mutation in the PH domain, tyrosine kin ase activity in BTK precipitates appeared to be decreased compared wit h control BLCL.