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BTK, A Novel Protein Tyrosine Kinase Mutated in X-Linked Agammaglobulinemia

  • Conference paper
Symposium in Immunology III

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Abstract

The immunoglobulin deficiency X-linked agammaglobulinemia (XLA; Bruton type, MIM 30030; gene symbol AGMX1) was described in 1952 (Bruton 1952). The disease is characterized by a B lymphocyte differentiation defect at the pre-B cell stage resulting in a pronounced decrease in the number of mature B lymphocytes and plasma cells (Siegal et al. 1971; Cooper and Lawton 1972; Preud’Homme et al. 1973; Conley 1985; Campana et al. 1990), whereas abnormalities in other cell lineages have not been found. The deficiency causes an increased susceptibility to mainly bacterial infections and the treatment consists of gammaglobulin replacement in combination with the administration of antibiotics in high doses. Obligate carriers are healthy with no signs of immunological defects. However, carrier B lymphocytes show nonrandom X inactivation, demonstrating that the normal gene product is needed for B cell proliferation or survival (Fearon et al. 1987; Conley and Puck 1988).

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References

  • Bruton OC (1952) Agammaglobulinemia. Pediatrics 9: 722–728

    PubMed  CAS  Google Scholar 

  • Campana D, Farrant J, Inamdar N, Webster ADB, Janossy G (1990) Phenotypic features and proliferative activity of B cell progenitors in X–linked agammaglobulinemia. J Immunol 145: 1675–1680

    PubMed  CAS  Google Scholar 

  • Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S (1991) Oncogenes and signal transduction. Cell 64: 281–302

    Article  PubMed  CAS  Google Scholar 

  • Cicchetti P, Mayer BJ, Thiel G, Baltimore D (1992) Identification of a protein that binds to the SH3 region of abl and is similar to Bcr and GAP-rho. Science 257: 803–806

    Article  PubMed  CAS  Google Scholar 

  • Conley ME (1985) B cells in patients with X-linked agammaglobulinemia. J Immunol 134: 3070–3074

    PubMed  CAS  Google Scholar 

  • Conley ME, Puck JM (1988) Carrier detection in typical and atypical X-linked agamma-globulinemia. J Pediatr 112: 688–693

    Article  PubMed  CAS  Google Scholar 

  • Cooper MD, Lawton AR (1972) Circulating B–cells in patients with immunodeficiency. Am J Pathol 69: 513–528

    PubMed  CAS  Google Scholar 

  • Desiderio S (1993) Becoming B cells. Nature 361: 202–203

    Article  PubMed  CAS  Google Scholar 

  • Fearon ER, Winkelstein JA, Civin CI, Pardoll DM, Vogelstein B (1987) Carrier detection in X-linked agammaglobulinemia by analysis of X-chromosome inactivation. N Engl J Med 316: 427–431

    Article  PubMed  CAS  Google Scholar 

  • Guioli S, Arveiler B, Bardoni B, Notarangelo LD, Panina P, Duse M, Ugazio A, Oberle I, de Saint Basile G, Mandel JL, Camerino G (1989) Close linkage of probe p212 (DXS178) to X-linked agammaglobulinemia. Hum Genet 84: 19–21

    CAS  Google Scholar 

  • Hanks SK, Quinn AM, Hunter T (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241: 42–52

    Article  PubMed  CAS  Google Scholar 

  • Kwan S-P, Kunkel L, Bruns G, Wedgwood RJ, Latt S, Rosen F (1986) Mapping of the X-linked agammaglobulinemia locus by use of restriction fragment length polymorphism. J Clin Invest 77: 649–652

    Article  PubMed  CAS  Google Scholar 

  • Kwan S-P, Terwilliger J, Parmley R, Raghu G, Sandkuyl LA, Ott J, Ochs H, Wedgwood R, Rosen F (1990) Identification of a closely linked DNA marker, DXS178, to further refine the X-linked agammaglobulinemia locus. Genomics 6: 238–242

    Article  PubMed  CAS  Google Scholar 

  • Lovett M, Kere J, Hinton L (1991) Direct selection: a method for the isolation of cDNAs encoded by large genomic regions. Proc Natl Acad Sei USA 88: 9628–9632

    Article  CAS  Google Scholar 

  • Malcolm S, de Saint Basile G, Arveiler B, Lau YL, Szabo P, Fischer A, Griscelli C, Debre M, Mandel JL, Callard RE, Robertson ME, Goodship JA, Pembrey ME, Levinsky RJ (1987) Close linkage of random DNA fragments from Xq21.3–22 to X-linked agammaglobulinemia ( XLA ). Hum Genet 77: 172–174

    Google Scholar 

  • Mano H, Ishikawa F, Nishida J, Hirai H, Takaku F (1990) A novel protein-tyrosine kinase, tec, is preferentially expressed in liver. Oncogene 5: 1781–1786

    PubMed  CAS  Google Scholar 

  • Mesink EJBM, Thompson A, Schot JOL, van de Greef WMM, Sandkuyl LA, Schuurman RKB (1986) Mapping of a gene for X-linked agammaglobulinemia and evidence for genetic heterogeneity. Hum Genet 73: 327–332

    Google Scholar 

  • O’Reilly M-A, Alterman LA, Zijlstra J, Malcolm S, Levinsky RJ, Kinnon C (1993) Pulsed–field gel electrophoresis and radiation hybrid mapping analyses enable the ordering of eleven DNA loci in Xq22. Genomics 15: 275–282

    Article  PubMed  Google Scholar 

  • Parimoo S, Patanjali SR, Shukla H, Chaplin DD, Weissman SM (1991) cDNA selection: efficient PCR approach for the selection of cDNAs encoded in large chromosomal DNA fragments. Proc Natl Acad Sei USA 88: 9623–9627

    Google Scholar 

  • Preud’Homme JL, Griscelli C, Seligmann M (1973) Immunoglobulins on the surface of lymphocytes in fifty patients with primary immunodeficiency diseases. Clin Immunol Immunopathol 1: 241–256 Siegal FP, Pernis B, Kunkel HG (1971) Lymphocytes in human immunodeficiency states: a study of membrane-associated immunoglobulins. Eur J Immunol 1: 482–486

    Google Scholar 

  • Siliciano JD, Morrow TA, Desiderio SV (1992) itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2. Proc Natl Acad Sei USA 89: 11194–11198

    Google Scholar 

  • Smith CIE, Baskin B, Humire-Greiff P, Jian-nian Z, Olsson PG, Maniar HS, Kjellen P, Lambris JD, Christensson B, Hammarström L, Bentley D, Vetrie D, Islam KB, Vorechovsky I, Sideras P (1994) Expression of Bruton’s agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and in plasma cells. J Immunol 152: 557–565

    Google Scholar 

  • Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, Sparkes RS, Kubagawa H, MohandasT, Quan S, Belmont JW, Cooper MD, Conley ME, Witte NO (1993) Deficient expression of a B-cell cytoplasmic tyrosine kinase in human X-linked agam-maglobulinemia. Cell 72: 279–290

    CAS  Google Scholar 

  • Vetrie D, Bobrow M, Harris A (1993a) Construction of a 5.2-megabase physical map of the human X chromosome at Xq22 using pulsed-field gel electrophoresis and yeast artificial chromosomes. Genomics 15: 631–642

    Article  PubMed  CAS  Google Scholar 

  • Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, Hammarström L, Kinnon C, Levinsky R, Bobrow M, Smith CIE, Bentley D (1993b) The gene involved in X– linked agammaglobulinemia is a member of the sre family of protein–tyrosine kinases. Nature 361: 226–233

    Article  PubMed  CAS  Google Scholar 

  • Vorechovsky I, Holland J, Sideras P, Dunham I, Hammarström L, Smith CIE, Bentley DR, Vetrie D (1993a) Isolation of cDNA clones mapping around DXS178: a search for human X-linked agammaglobulinemia gene using yeast artificial chromosomes, cosmids and direct cDNA selection. Immunodeficiency 4: 221–224

    PubMed  CAS  Google Scholar 

  • Vorechovsky I, Jian-nian Z, Bentley D, Vetrie D, Björkander J, Hammarström L, Smith CIE (1993b) Molecular diagnosis of X–linked agammaglobulinemia. Lancet 341: 1153

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. C. I. E. Smith
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  2. I. Vorechovsky
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  3. L. Hammarström
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  4. D. Vetrie
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  5. P. Sideras
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Editor information

Editors and Affiliations

  1. Institut für Immunologie, Universität Wien, Borschkegasse 8a, A-1090, Wien, Austria

    Martha M. Eibl

  2. Abteilung für Hämatologie, Johannes Gutenberg Universität, Langenbeckstr. 1, D-55131, Mainz, Germany

    Christoph Huber

  3. Division of Hematology, III. Department of Internal Medicine, Johannes Gutenberg University, Medical Center, Langenbeckstr. 1, D-55131, Mainz, Germany

    Christoph Huber

  4. Abteilung für Rheumatologie und Klinische Immunologie, Medizinische Universitätsklinik, Hugstetter Str. 55, D-79106, Freiburg, Germany

    Hans H. Peter

  5. Pädiatrische Pneumologie und Immunologie, Universitätsklinikum Rudolf Virchow Standort Charlottenburg, Heubnerweg 6, D-14059, Berlin, Germany

    Ulrich Wahn

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© 1994 Springer-Verlag Berlin Heidelberg

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Smith, C.I.E., Vorechovsky, I., Hammarström, L., Vetrie, D., Sideras, P. (1994). BTK, A Novel Protein Tyrosine Kinase Mutated in X-Linked Agammaglobulinemia. In: Eibl, M.M., Huber, C., Peter, H.H., Wahn, U. (eds) Symposium in Immunology III. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78438-5_7

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  • DOI: https://doi.org/10.1007/978-3-642-78438-5_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-57126-1

  • Online ISBN: 978-3-642-78438-5

  • eBook Packages: Springer Book Archive

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