EXPRESSION OF BRUTONS TYROSINE KINASE PROTEIN WITHIN THE B-CELL LINEAGE

被引:93
作者
GENEVIER, HC
HINSHELWOOD, S
GASPAR, HB
RIGLEY, KP
BROWN, D
SAELAND, S
ROUSSET, F
LEVINSKY, RJ
CALLARD, RE
KINNON, C
LOVERING, RC
机构
[1] INST CHILD HLTH,MOLEC IMMUNOL UNIT,LONDON WC1N 1EH,ENGLAND
[2] INST CHILD HLTH,CELLULAR IMMUNOL UNIT,LONDON WC1N 1EH,ENGLAND
[3] SCHERING PLOUGH CORP,CTR RECH,DARDILLY,FRANCE
[4] CELLTECH LTD,SLOUGH SL1 4EN,BERKS,ENGLAND
基金
英国惠康基金;
关键词
B CELLS; BRUTONS TYROSINE KINASE; IMMUNODEFICIENCY; TYROSINE KINASE; X-LINKED AGAMMAGLOBULINEMIA;
D O I
10.1002/eji.1830241228
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:3100 / 3105
页数:6
相关论文
共 24 条
[1]   MUTATION DETECTION IN THE X-LINKED AGAMMAGLOBULINEMIA GENE, BTK, USING SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS [J].
BRADLEY, LAD ;
SWEATMAN, AK ;
LOVERING, RC ;
JONES, AM ;
MORGAN, G ;
LEVINSKY, RJ ;
KINNON, C .
HUMAN MOLECULAR GENETICS, 1994, 3 (01) :79-83
[2]  
BRUTON OC, 1952, PEDIATRICS, V9, P722
[3]  
CALLARD RE, 1991, CYTOKINES PRACTICAL, P121
[4]  
CAMPANA D, 1990, J IMMUNOL, V145, P1675
[5]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[6]  
CONLEY ME, 1985, J IMMUNOL, V134, P3070
[7]   HUMAN-IMMUNOGLOBULIN C-LAMBDA-6 GENE ENCODES THE KERN+OZ- LAMBDA-CHAIN AND C-LAMBDA-4 AND C-LAMBDA-5 ARE PSEUDOGENES [J].
DARIAVACH, P ;
LEFRANC, G ;
LEFRANC, MP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (24) :9074-9078
[8]   MUTATION ANALYSIS OF THE BRUTONS TYROSINE KINASE GENE IN X-LINKED AGAMMAGLOBULINEMIA - IDENTIFICATION OF A MUTATION WHICH AFFECTS THE SAME CODON AS IS ALTERED IN IMMUNODEFICIENT XID MICE [J].
DEWEERS, M ;
MENSINK, RGJ ;
KRAAKMAN, MEM ;
SCHUURMAN, RKB ;
HENDRIKS, RW .
HUMAN MOLECULAR GENETICS, 1994, 3 (01) :161-166
[9]   THE BRUTON 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 [J].
DEWEERS, M ;
VERSCHUREN, MCM ;
KRAAKMAN, MEM ;
MENSINK, RGJ ;
SCHUURMAN, RKB ;
VANDONGEN, JJM ;
HENDRIKS, RW .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (12) :3109-3114
[10]  
FORT P, 1985, NUCLEIC ACIDS RES, V13, P31