EXPRESSION OF BRUTONS TYROSINE KINASE PROTEIN WITHIN THE B-CELL LINEAGE
EXPRESSION OF BRUTONS TYROSINE KINASE PROTEIN WITHIN THE B-CELL LINEAGE
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DOI：
10.1002/eji.1830241228
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发表时间：
1994-12-01
影响因子：
5.4
通讯作者：
LOVERING, RC
中科院分区：
文献类型：
--
作者：
GENEVIER, HC;HINSHELWOOD, S;LOVERING, RC
通常在B细胞中表达的编码布鲁顿酪氨酸激酶（Btk）的基因缺陷导致X连锁无丙种球蛋白血症（XLA）。XLA的表型特征在于缺乏循环B细胞和免疫球蛋白。已经表明，B细胞从前B细胞阶段成熟到更成熟的阶段依赖于该基因的适当表达。Btk mRNA在B细胞和髓样细胞中表达，但与B细胞成熟相关的蛋白质表达尚未确定。此外，迄今为止仅在人EB病毒转化的B细胞系和鼠脾细胞和B细胞系中研究了Btk蛋白的表达。我们已经开发了一种抗血清，它可以识别人Btk蛋白，并显示正常人扁桃体B细胞、外周血单核细胞和骨髓细胞表达该蛋白，而扁桃体衍生的T细胞不表达。我们还表明，该蛋白存在于早期和成熟的人B细胞系，但在终末分化的浆细胞系中是不存在的。此外，在来源于两名具有确定的Btk基因突变并患有XLA的患者的三种B谱系细胞系中表达减少或不存在。
Defects in the gene encoding Bruton's tyrosine kinase (Btk), normally expressed in B cells, cause X-linked agammaglobulinemia (XLA). The phenotype of XLA is characterized by a lack of circulating B cells and immunoglobulin. It has been suggested that B cell maturation from the pre-B cell stage to more mature stages is dependent on the appropriate expression of this gene. The Btk mRNA is expressed in B cells and myeloid cells, but protein expression in relation to B cell maturation has not been determined. Moreover, expression of the Btk protein has so far only been investigated in human Epstein-Barr virus-transformed B cell lines, and in murine splenocytes and B cell lines. We have developed an antiserum which recognizes the human Btk protein and shown that normal human tonsillar B cells, peripheral blood monocytes and myeloid cells express the protein, whereas tonsil-derived T cells do not. We also show that the protein is present in early and mature human B cell lines, but is absent in terminally differentiated plasma cell lines. Furthermore, expression is reduced or absent in three B lineage cell lines derived from two patients with defined genetic mutations in Btk and suffering from XLA.