Journal of Clinical Immunology

, Volume 11, Issue 5, pp 262–267 | Cite as

Expression of immunoglobulin genes in common variable immunodeficiency

  • Hideo Kaneko
  • Naomi Kondo
  • Fumiaki Motoyoshi
  • Seiji Mori
  • Yuki Kobayashi
  • Yuko Inoue
  • Tadao Orii
Original Articles


Five common variable immunodeficiency (CVI) patients were analyzed for expression of immunoglobulin (Ig) genes. In the pokeweed mitogen (PWM)-induced Ig-production assay, the combination of T and B cells showed that all patients' T cells had normal helper functions and all patients' B cells had profound defects. The defective B-cell maturation stages based on their Ig gene expression patterns were variable. One of five patients showed normal μ-chain gene expression and nearly normal IgM production, but neither IgG nor IgA production, which suggested that this patient's B-cell defects might lie on a μ- to γ or μ- to α class-switch stage. B cells in another patient showed low μ-chain gene expression and low IgM production, but an Ig enhancer region, which is an important region for expression of Ig genes, was intact. Thus, this patient might have a transacting factor defect which interacts with the Ig enhancer region. The other three patients showed no μ-chain gene expression and no IgM production. Thus, their B-cell defects lay on the B-cell maturation stage, similar to X-linked agammaglobulinemia. These results showed that primary B-cell defects in CVI occurred at several B-cell differentiation stages, which could be recognized by expression of Ig genes.

Key words

Common variable immunodeficiency (CVI) μ messenger RNA interleukins Ig enhancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Geha RS, Schneeberger E, Merler E, Rosen FS: Heterogeneity of “acquired” or common variable agammaglobulinemia. N Engl J Med 291:1–6, 1974Google Scholar
  2. 2.
    Jelinek DF, Splawski JB, Lipsky TE: The roles of interleukin 2 and interferon γ in human B cell activation, growth and differentiation. Eur J Immunol 16:925–931, 1986Google Scholar
  3. 3.
    Defrance T, Vanbervliet B, Pene J, Branchereau J: Human recombinant IL-4 induces activated B lymphocytes to produce IgG and IgM. J Immunol 141:2000–2005, 1988Google Scholar
  4. 4.
    Muraguchi A, Hirano T, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T: The essential role of B cell stimulatory factor 2 (BSF-1/IL-6) for the terminal differentiation of B cells. J Exp Med 167:332–344, 1988Google Scholar
  5. 5.
    Farrant J, Bryant A, Almandoz F, Spickett G, Evans SW, Webster ADB: B cell function in acquired “commonvariable” hypogammaglobulinemia: Proliferative responses to lymphokines. Clin Immunol Immunopathol 51:196–204, 1989Google Scholar
  6. 6.
    North ME, Webster ADB, Farrant J: Role of interleukin-2 and interleukin-6 in the mitogen responsiveness of T cells from patients with “common-variable” hypogammaglobulinaemia. Clin Exp Immunol 81:412–416, 1990Google Scholar
  7. 7.
    Sneller MC, Strober W: Abnormality of lymphokine gene expression in patients with common variable immunodeficiency. J Immunol 144:3762–3769, 1990Google Scholar
  8. 8.
    Sleasman JW, Tedder TF, Barrett DJ: Combined immuno-deficiency due to the selective absence of CD4 inducer T lymphocytes. Clin Immunol Immunopathol 55:401–417, 1990Google Scholar
  9. 9.
    Disanto JP, Keever CA, Small TN, Nichols GL, O'Reilly RJ, Flomenberg N: Absence of interleukin 2 production in a severe combined immunodeficiency disease syndrome with T cells. J Exp Med 171:1697–1704, 1990Google Scholar
  10. 10.
    Kaneko H, Nakashima M, Kudo A, Iwakiri R, Harada M, Watanabe T: Selective IgG deficiency with a transcriptional disorder of the γ switching region gene and the IL-4 gene. Int Immunol 2:661–668, 1990Google Scholar
  11. 11.
    Gills SD, Morrison SL, Oi VT, Tonegawa S: A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 33:717–728, 1983Google Scholar
  12. 12.
    Banerji J, Olson L, Shaffner W: A lymphocytes-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell 33:729–740, 1983Google Scholar
  13. 13.
    Bergman Y, Rice D, Grosschedl R, Baltimore D: Two regulatory elements for immunoglobulin gene expression. Proc Natl Acad Sci USA 81:7041–7045, 1984Google Scholar
  14. 14.
    Mason JQ, Williams GT, Neuberger MS: Transcription cell type specificity is conferred by an immunoglobulin VH gene promoter that induces a functional consensus sequence. Cell 41:479–487, 1985Google Scholar
  15. 15.
    Maeda H, Kitamura D, Kudo A, Araki K, Watanabe T: Transacting nuclear proteins responsible for induction of rearranged human immunoglobulin heavy chain gene. Cell 45:25–33, 1986Google Scholar
  16. 16.
    Maeda H, Araki K, Kitamura D, Wang J, Watanabe T: Nuclear factors binding to the human immunoglobulin heavy-chain gene enhancer. Nucl Acids Res 15:2851–2869, 1987Google Scholar
  17. 17.
    Araki K, Maeda H, Wang J, Kitamura D, Watanabe T: Purification of a nuclear trans-acting factor involved in the regulated transcription of a human immunoglobulin heavy chain gene. Cell 53:723–730, 1988Google Scholar
  18. 18.
    Reith W, Satola S, Sanchez CH, Amaldi I, Grospierre BL, Griscelli C, Hadam MR, Mach B: Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X. Cell 53:897–906, 1988Google Scholar
  19. 19.
    Kondo N, Orii T, Uetake H: Competence of B cells for T-cell help in pokeweed mitogen-induced immunoglobulin production. Clin Immunol Immunopathol 26:192–200, 1983Google Scholar
  20. 20.
    Kitamura D, Kaneko H, Miyagoe Y, Ariyasu T, Watanabe T: Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage. Nucl Acids Res 17:9367–9379, 1989Google Scholar
  21. 21.
    Takahashi N, Nakai S, Honjo T: Cloning of human immunoglobulin μ gene and comparison with mouse μ gene. Nucl Acids Res 8:5893–5901, 1980Google Scholar
  22. 22.
    Rabbitts TH, Foster A, Baer R, Hamlyn PH: Transcription enhancer identified near the human Cμ immunoglobulin heavy chain gene is unavailable to the translocated c-myc gene in a Burkitt lymphoma. Nature 306:806–809, 1983Google Scholar
  23. 23.
    Mills FC, Fisher LM, Kuroda L, Ford AM, Gould HJ: DNase I hypersensitive sites in the chromatin of human μ immunoglobulin heavy-chain genes. Nature 306:809–812, 1983Google Scholar
  24. 24.
    Akahori Y, Kurosawa Y, Kamachi Y, Torii S, Matsuoka H: Presence of immunoglobulin (Ig) M and IgG double isotype-bearing cells and defects of switch recombination in hyper IgM immunodeficiency. J Clin Invest 85:1722–1727, 1990Google Scholar
  25. 25.
    Sherr E, Adelman DC, Saxon A, Gilly M, Wall R, Sidell N: Retinoic acid induces the differentiation of B cell hybridomas from patients with common variable immunodeficiency. J Exp Med 168:55–71, 1988Google Scholar
  26. 26.
    Campana D, Farrant J, Inamdar N, Webster ADB, Janossy G: Phenotypic features and proliferative activity of B cell progenitors in X-linked agammaglobulinemia. J Immunol 145:1675–1680, 1990Google Scholar
  27. 27.
    Schwaber J, Molgaard H, Orkin SH, Gould HJ, Rosen FS: Early pre-B cells from normal and X-linked agammaglobulinaemia produce Cμ without an attached VH region. Nature 304:355–358, 1983Google Scholar
  28. 28.
    Schwaber J, Koenig N, Giard J: Correction of the molecular defects in B lymphocytes from X-linked agammaglobulinemia by cell fusion. J Clin Invest 82:1471–1476, 1988Google Scholar
  29. 29.
    Ferrier P, Krippl B, Blackwell TK, Furley AJ, Suh H, Winoto A, Cook WD, Hood L, Costantini F, Alt FW: Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate. EMBO 9:117–125, 1990Google Scholar
  30. 30.
    Schatz DG, Oettinger MA, Baltimore D: The V(D)J recombination activating gene, RAG-1. Cell 55:1035–1048, 1989Google Scholar
  31. 31.
    Oettinger MA, Schatz DG, Gorka C, Baltimore D: RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248:1517–1523, 1990Google Scholar

Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Hideo Kaneko
    • 1
  • Naomi Kondo
    • 1
  • Fumiaki Motoyoshi
    • 1
  • Seiji Mori
    • 1
  • Yuki Kobayashi
    • 1
  • Yuko Inoue
    • 1
  • Tadao Orii
    • 1
  1. 1.Department of PediatricsGifu University School of MedicineGifuJapan

Personalised recommendations