THE BRUTON TYROSINE KINASE GENE IS EXPRESSED THROUGHOUT B-CELL DIFFERENTIATION, FROM EARLY PRECURSOR B-CELL STAGES PRECEDING IMMUNOGLOBULINGENE REARRANGEMENT UP TO MATURE B-CELL STAGES

X-linked agammaglobulinemia (XLA) is an immunodeficiency disease in ma n, resulting from an arrest in early B cell differentiation. The gene defective in XLA has recently been identified and encodes a cytoplasmi c protein tyrosine kinase, named Bruton's tyrosine kinase (btk), essen tial for cell differentiation and proliferation at the transition from pre-B to later B cell stages. In this study we investigated btk expre ssion by Northern blotting experiments in a series of human (precursor -) B cell lines, acute lymphoblastic leukemias and plasmacytomas. btk was found to be already expressed in very early stages of B cell diffe rentiation, even prior to immunoglobulin (Ig) heavy (H) or light (L) c hain gene rearrangements. Transcripts were also detected at the pre-B cell stage and in mature B cells, irrespective of the Ig H chain class expressed. Approximately at the transition from mature B cells to pla sma cells, expression of the btk gene is down-regulated. In addition, the btk gene was found to be expressed in myeloid cell lines and acute myeloid leukemias. btk expression in myeloid cells is probably not a prerequisite for myeloid differentiation, since myeloid cells in XLA p atients seem not to be affected. No btk expression was found in T-line age cells. The btk expression profile, i.e. from early precursor-B cel l stages preceding Ig rearrangement up to mature B cells, supports the hypothesis that the XLA defect resides in a critical step of B cell d evelopment which is independent of the Ig gene recombination machinery .