Skip to main content
SpringerLink
Log in
Book cover

Hot Topics in Infection and Immunity in Children VII pp 183–196Cite as

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

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((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.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  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.

    PubMed  Google Scholar 

  2. Hendriks RW, Middendorp S. The pre-BCR checkpoint as a cell-autonomous proliferation switch. Trends Immunol. 2004;25(5):249–56.

    Article  CAS  PubMed  Google Scholar 

  3. Carter RH, Fearon DT. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science. 1992;256(5053):105–7.

    Article  CAS  PubMed  Google Scholar 

  4. van Noesel CJ, Lankester AC, van Lier RA. Dual antigen recognition by B cells. Immunol Today. 1993;14(1):8–11.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  6. Honjo T, Kinoshita K, Muramatsu M. Molecular mechanism of class switch recombination: linkage with somatic hypermutation. Annu Rev Immunol. 2002;20:165–96.

    Article  CAS  PubMed  Google Scholar 

  7. Odegard VH, Schatz DG. Targeting of somatic hypermutation. Nat Rev Immunol. 2006;6(8):573–83.

    Article  CAS  PubMed  Google Scholar 

  8. Cerutti A. The regulation of IgA class switching. Nat Rev Immunol. 2008;8(6):421–34.

    Article  CAS  PubMed  Google Scholar 

  9. Weill JC, Weller S, Reynaud CA. Human marginal zone B cells. Annu Rev Immunol. 2009;27:267–85.

    Article  CAS  PubMed  Google Scholar 

  10. Mond JJ, Vos Q, Lees A, Snapper CM. T cell independent antigens. Curr Opin Immunol. 1995;7(3):349–54.

    Article  CAS  PubMed  Google Scholar 

  11. Peng SL. Signaling in B cells via Toll-like receptors. Curr Opin Immunol. 2005;17(3):230–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  14. Pan-Hammarstrom Q, Hammarstrom L. Antibody deficiency diseases. Eur J Immunol. 2008;38(2):327–33.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  25. Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101–21.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  35. Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. 2008;28(Suppl 1):S42–S45.

    Article  PubMed  Google Scholar 

  36. Lopes-da-Silva S, Rizzo LV. Autoimmunity in common variable immunodeficiency. J Clin Immunol. 2008;28(Suppl 1):S46–S55.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

    Mirjam van der Burg & Jacques J.M. van Dongen

  2. Department of Immunology, University Medical Center, Rotterdam, The Netherlands

    Menno C. van Zelm

  3. Department of Pediatrics, University Medical Center, Rotterdam, The Netherlands

    Gertjan J.A. Driessen

Authors
  1. Mirjam van der Burg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Menno C. van Zelm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gertjan J.A. Driessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacques J.M. van Dongen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jacques J.M. van Dongen .

Editor information

Editors and Affiliations

  1. Royal Children's Hospital, Dept. Pediatrics, University of Melbourne, Flemington Road, Parkville, 3052, Victoria, Australia

    Nigel Curtis

  2. Institute of Child Life and Health, UBHT Education Centre, University of Bristol, Upper Maudlin Street, Bristol, BS2 8AE, United Kingdom

    Adam Finn

  3. University of Oxford, Level 4,John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom

    Andrew J. Pollard

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

van der Burg, M., van Zelm, M.C., Driessen, G.J., van Dongen, J.J. (2011). Dissection of B-Cell Development to Unravel Defects in Patients with a Primary Antibody Deficiency. In: Curtis, N., Finn, A., Pollard, A. (eds) Hot Topics in Infection and Immunity in Children VII. Advances in Experimental Medicine and Biology, vol 697. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7185-2_13

Download citation

Publish with us

Policies and ethics

Search

Navigation