Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and plasma cells.
The gene mutated in the human disease, X-linked agammaglobulinemia (XLA), is related to the Src gene family of cytoplasmic protein-tyrosine kinases and is designated Btk (Bruton's agammaglobulinemia tyrosine kinase; formerly Atk/Bpk; the human gene is denoted BTK, using capital letters according to the kinase nomenclature). We have recently reported that this gene is expressed in B lymphocytes and that the specific mRNA was undetectable in T cells using Northern blotting. Further analyses of different sources of B and T lymphocytes confirmed this pattern. However, BTK transcripts were undetectable in four plasmacytoma lines. Moreover, as virtually normal amounts of BTK transcripts were found in PBMC from two patients carrying a point mutation in BTK, despite low B cell numbers, we anticipated that the gene would also be expressed in cells of other lineages. The erythroleukemia cell line K-562, the promyelocytic line HL-60 and the histiocytic lymphoma line U-937 were found to have BTK mRNA levels comparable to B cells. BTK mRNA was also detected in monocytes from healthy donors as well as in the human immature basophilic cell line KU812, in the human mast cell leukemia cell line HMC-1 and in the CD34 expressing myeloblast KG-1. A similar expression pattern was obtained when BTK protein was analyzed by immunoprecipitation and Western blotting. Using a polymerase chain reaction-based analysis, a small amount (less than 1% of the level in B cells) of BTK mRNA was identified in T lymphocytes. Our findings are compatible with a general expression of the BTK gene in hematopoietic cells, except in T lymphocytes and plasma cells, in which the transcript level is selectively down-regulated.
Smith
C I
CI
Center for BioTechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
Baskin
B
B
Humire-Greiff
P
P
Zhou
J N
JN
Olsson
P G
PG
Maniar
H S
HS
Kjellén
P
P
Lambris
J D
JD
Christensson
B
B
Hammarström
L
L
D000361:Agammaglobulinemia / Q000201:enzymology*; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology; D001483:Base Sequence; D001853:Bone Marrow / Q000201:enzymology; D002454:Cell Differentiation; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008407:Mast Cells / Q000201:enzymology; D008969:Molecular Sequence Data; D010703:Phorbol Esters / Q000494:pharmacology; D010950:Plasma Cells / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology*; D014212:Tretinoin / Q000494:pharmacology; D014960:X Chromosome
D017931:DNA Primers; D010703:Phorbol Esters; D012333:RNA, Messenger; D014212:Tretinoin; D011505:Protein-Tyrosine Kinases