The Bruton's tyrosine kinase gene is expressed throughout B cell differentiation, from early precursor B cell stages preceding immunoglobulin gene rearrangement up to mature B cell stages.
X-linked agammaglobulinemia (XLA) is an immunodeficiency disease in man, resulting from an arrest in early B cell differentiation. The gene defective in XLA has recently been identified and encodes a cytoplasmic protein tyrosine kinase, named Bruton's tyrosine kinase (btk), essential for cell differentiation and proliferation at the transition from pre-B to later B cell stages. In this study we investigated btk expression 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 differentiation, even prior to immunoglobulin (Ig) heavy (H) or light (L) chain 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 plasma 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 patients seem not to be affected. No btk expression was found in T-lineage cells. The btk expression profile, i.e. from early precursor-B cell stages preceding Ig rearrangement up to mature B cells, supports the hypothesis that the XLA defect resides in a critical step of B cell development which is independent of the Ig gene recombination machinery.
de Weers
M
M
Department of Immunohematology, University Hospital, The Netherlands.
Verschuren
M C
MC
Kraakman
M E
ME
Mensink
R G
RG
Schuurman
R K
RK
van Dongen
J J
JJ
Hendriks
R W
RW
D000361:Agammaglobulinemia / Q000235:genetics*; D001402:B-Lymphocytes / Q000201:enzymology* / Q000502:physiology; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D015870:Gene Expression; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D008040:Genetic Linkage; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D004854:Herpesvirus 4, Human; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000201:enzymology; D014960:X Chromosome
D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases