Advertisement

Dissection of B-Cell Development to Unravel Defects in Patients with a Primary Antibody Deficiency

  • Mirjam van der Burg
  • Menno C. van Zelm
  • Gertjan J.A. Driessen
  • Jacques J.M. van Dongen
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 697)

Abstract

The cells of the adaptive immune response (B and T lymphocytes) are powerful players in the immune system. Each lymphocyte creates a unique receptor for recognition of pathogens during precursor differentiation in bone marrow or thymus. Together, this results in a large repertoire of antigen receptors with the potential to recognize many different pathogens specifically. On top of this broad repertoire, the lymphocytes that actually recognize antigen are capable of undergoing enormous clonal proliferation, thereby generating huge numbers of daughter cells with the potential to recognize the same pathogen. This clonal expansion generates effector cells for a strong response and long-term memory in the form of memory B and T cells and immunoglobulin (Ig)-producing plasma cells.

Keywords

Germinal Center Class Switch Recombination Antibody Deficiency CVID Patient Primary Antibody Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    van Zelm MC, van der Burg M, de Ridder D, Barendregt BH, de Haas EF, Reinders MJ et al. Ig gene rearrangement steps are initiated in early human precursor B cell subsets and correlate with specific transcription factor expression. J Immunol. 2005;175(9):5912–22.PubMedGoogle Scholar
  2. 2.
    Hendriks RW, Middendorp S. The pre-BCR checkpoint as a cell-autonomous proliferation switch. Trends Immunol. 2004;25(5):249–56.CrossRefPubMedGoogle Scholar
  3. 3.
    Carter RH, Fearon DT. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science. 1992;256(5053):105–7.CrossRefPubMedGoogle Scholar
  4. 4.
    van Noesel CJ, Lankester AC, van Lier RA. Dual antigen recognition by B cells. Immunol Today. 1993;14(1):8–11.CrossRefPubMedGoogle Scholar
  5. 5.
    Fearon DT, Carroll MC. Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu Rev Immunol. 2000;18:393–422.CrossRefPubMedGoogle Scholar
  6. 6.
    Honjo T, Kinoshita K, Muramatsu M. Molecular mechanism of class switch recombination: linkage with somatic hypermutation. Annu Rev Immunol. 2002;20:165–96.CrossRefPubMedGoogle Scholar
  7. 7.
    Odegard VH, Schatz DG. Targeting of somatic hypermutation. Nat Rev Immunol. 2006;6(8):573–83.CrossRefPubMedGoogle Scholar
  8. 8.
    Cerutti A. The regulation of IgA class switching. Nat Rev Immunol. 2008;8(6):421–34.CrossRefPubMedGoogle Scholar
  9. 9.
    Weill JC, Weller S, Reynaud CA. Human marginal zone B cells. Annu Rev Immunol. 2009;27:267–85.CrossRefPubMedGoogle Scholar
  10. 10.
    Mond JJ, Vos Q, Lees A, Snapper CM. T cell independent antigens. Curr Opin Immunol. 1995;7(3):349–54.CrossRefPubMedGoogle Scholar
  11. 11.
    Peng SL. Signaling in B cells via Toll-like receptors. Curr Opin Immunol. 2005;17(3):230–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME et al. Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood. 2004;104(12):3647–54.CrossRefPubMedGoogle Scholar
  13. 13.
    Comans-Bitter WM, de Groot R, van den Beemd R, Neijens HJ, Hop WC, Groeneveld K et al. Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations. J Pediatr. 1997;130(3):388–93.CrossRefPubMedGoogle Scholar
  14. 14.
    Pan-Hammarstrom Q, Hammarstrom L. Antibody deficiency diseases. Eur J Immunol. 2008;38(2):327–33.CrossRefPubMedGoogle Scholar
  15. 15.
    Peron S, Metin A, Gardes P, Alyanakian MA, Sheridan E, Kratz CP et al. Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination. J Exp Med. 2008;205(11):2465–72.CrossRefPubMedGoogle Scholar
  16. 16.
    Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Bohm J et al. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci U S A. 2009;106(33):13945–50.CrossRefPubMedGoogle Scholar
  17. 17.
    Conley ME, Dobbs AK, Farmer DM, Kilic S, Paris K, Grigoriadou S et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009;27:199–227.CrossRefPubMedGoogle Scholar
  18. 18.
    Noordzij JG, de Bruin-Versteeg S, Comans-Bitter WM, Hartwig NG, Hendriks RW, de Groot R et al. Composition of precursor B-cell compartment in bone marrow from patients with X-linked agammaglobulinemia compared with healthy children. Pediatr Res. 2002;51(2):159–68.CrossRefPubMedGoogle Scholar
  19. 19.
    van Zelm MC, Geertsema C, Nieuwenhuis N, de Ridder D, Conley ME, Schiff C et al. Gross deletions involving IGHM, BTK, or Artemis: a model for genomic lesions mediated by transposable elements. Am J Hum Genet. 2008;82(2):320–32.CrossRefPubMedGoogle Scholar
  20. 20.
    Minegishi Y, Rohrer J, Coustan-Smith E, Lederman HM, Pappu R, Campana D et al. An essential role for BLNK in human B cell development. Science. 1999;286(5446):1954–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Kanegane H, Agematsu K, Futatani T, Sira MM, Suga K, Sekiguchi T et al. Novel mutations in a Japanese patient with CD19 deficiency. Genes Immun. 2007;8(8):663–70.CrossRefPubMedGoogle Scholar
  22. 22.
    van Zelm MC, Reisli I, van der Burg M, Castaño D, van Noesel CJM, van Tol MJD et al. An Antibody-Deficiency Syndrome Due to Mutations in the CD19 Gene. N Engl J Med. 2006;354(18):1901–12.CrossRefPubMedGoogle Scholar
  23. 23.
    van Zelm MC, Smet J, Adams B, Mascart F, Schandene L, Janssen F et al. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest 2010;120(4):1265–74.CrossRefGoogle Scholar
  24. 24.
    Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins NA, Copeland NG et al. CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science. 1993;259(5097):990–3.CrossRefPubMedGoogle Scholar
  25. 25.
    Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101–21.PubMedGoogle Scholar
  26. 26.
    Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina AR, Loubser M et al. Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM. Proc Natl Acad Sci U S A. 2001;98(22):12614–19.CrossRefPubMedGoogle Scholar
  27. 27.
    Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell. 2000;102(5):565–75.CrossRefPubMedGoogle Scholar
  28. 28.
    Weller S, Faili A, Garcia C, Braun MC, Le Deist FF, de Saint Basile GG et al. CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans. Proc Natl Acad Sci U S A. 2001;98(3):1166–70.CrossRefPubMedGoogle Scholar
  29. 29.
    He B, Xu W, Santini PA, Polydorides AD, Chiu A, Estrella J et al. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity. 2007;26(6):812–26.CrossRefPubMedGoogle Scholar
  30. 30.
    Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37(8):829–34.CrossRefPubMedGoogle Scholar
  31. 31.
    Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Drager R et al. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol. 2003;4(3):261–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Salzer U, Chapel HM, Webster AD, Pan-Hammarstrom Q, Schmitt-Graeff A, Schlesier M et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37(8):820–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Zhang L, Radigan L, Salzer U, Behrens TW, Grimbacher B, Diaz G et al. Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes. J Allergy Clin Immunol. 2007;120(5):1178–85.CrossRefPubMedGoogle Scholar
  34. 34.
    Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277–86.CrossRefPubMedGoogle Scholar
  35. 35.
    Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. 2008;28(Suppl 1):S42–S45.CrossRefPubMedGoogle Scholar
  36. 36.
    Lopes-da-Silva S, Rizzo LV. Autoimmunity in common variable immunodeficiency. J Clin Immunol. 2008;28(Suppl 1):S46–S55.CrossRefPubMedGoogle Scholar
  37. 37.
    Chua I, Quinti I, Grimbacher B. Lymphoma in common variable immunodeficiency: interplay between immune dysregulation, infection and genetics. Curr Opin Hematol. 2008;15(4):368–74.CrossRefPubMedGoogle Scholar
  38. 38.
    Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111(1):77–85.CrossRefPubMedGoogle Scholar
  39. 39.
    Andersen P, Permin H, Andersen V, Schejbel L, Garred P, Svejgaard A et al. Deficiency of somatic hypermutation of the antibody light chain is associated with increased frequency of severe respiratory tract infection in common variable immunodeficiency. Blood. 2005;105(2):511–17.CrossRefPubMedGoogle Scholar
  40. 40.
    van Zelm MC, Szczepanski T, van der Burg M, van Dongen JJ. Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion. J Exp Med. 2007;204(3):645–55.CrossRefPubMedGoogle Scholar
  41. 41.
    Driessen GJA, van Zelm MC, Van Dongen JJM, Hartwig NG, van Hagen PM, van der Burg M. New phenotype in patients with common variable immunodeficiency characterized by increased proliferation of naïve mature B-cells. Eur J Immunol. 2009;39(S1):S1–6.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Mirjam van der Burg
    • 1
  • Menno C. van Zelm
    • 2
  • Gertjan J.A. Driessen
    • 3
  • Jacques J.M. van Dongen
    • 1
  1. 1.Department of ImmunologyErasmus MC, University Medical CenterRotterdamThe Netherlands
  2. 2.Department of ImmunologyUniversity Medical CenterRotterdamThe Netherlands
  3. 3.Department of PediatricsUniversity Medical CenterRotterdamThe Netherlands

Personalised recommendations