How Do You Say “B-Cell Biology” In “Vaccinology”: Translational Research In the NIAID

  • Susan K. Pierce
Chapter
First Online:
Part of the Infectious Disease book series (ID)

Abstract

B-cell antibody responses play a key role in protection from a variety of infectious diseases. It has long been appreciated that, to a large extent, protection relies on the ability of B cells to encode an immunological memory, namely, the ability to respond more quickly and robustly to reinfection with a pathogen. In fact, all vaccines are predicated on the ability to induce long-lasting immunological memory. For antibody responses, memory is encoded, in part, in long-lived, high-affinity memory B cells MBCs that can be rapidly activated by pathogen antigens to give rise to antibody-secreting cells and long-lived plasma cells that constitutively secrete antibodies maintaining a protective level of pathogen-specific antibodies [1]. Clearly, our ability to design potent, effective vaccines would profit from a detailed understanding of the mechanisms that underlie the activation of B cells in a nonimmune, immunologically-naïve individual to yield memory B cells and long-lived plasma cells.

Keywords

Malaria Infection Malaria Vaccine Multivalent Antigen Immunoreceptor Tyrosine Activation Motif Monovalent Antigen 
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.
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Notes

Acknowledgements

This work was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases.

References

  1. 1.
    Crotty S & Ahmed R (2004) Immunological memory in humans. Semin Immunol 16: 197–203PubMedCrossRefGoogle Scholar
  2. 2.
    Campbell KS (1999) Signal transduction from the B cell antigen-receptor. Curr Opin Immunol 11: 256–264PubMedCrossRefGoogle Scholar
  3. 3.
    Kurosaki T (1999) Genetic analysis of B cell antigen receptor signaling. Annu Rev Immunol 17: 555–592PubMedCrossRefGoogle Scholar
  4. 4.
    Davis MM (2008) A prescription for human immunology. Immunity 29: 835–838PubMedCrossRefGoogle Scholar
  5. 5.
    Langhorne J, Ndungu FM, Sponaas AM, et al (2008) Immunity to malaria: more questions than answers. Nat Immunol 9: 725–732PubMedCrossRefGoogle Scholar
  6. 6.
    Reth M (1992) Antigen receptors on B lymphocytes. Annu Rev Immunol 10: 97–121PubMedCrossRefGoogle Scholar
  7. 7.
    Dal Porto JM, Gauld SB, Merrell KT, et al (2004) B cell antigen receptor signaling 101. Mol Immunol 41: 599–613PubMedCrossRefGoogle Scholar
  8. 8.
    Brezski RJ & Monroe JG (2008) B-cell receptor. Adv Exp Med Biol 640: 12–21PubMedCrossRefGoogle Scholar
  9. 9.
    Metzger H (1992) Transmembrane signaling: the joy of aggregation. J Immunol 149: 1477–1487PubMedGoogle Scholar
  10. 10.
    Wilson IA & Stanfield RL (1994) Antibody-antigen interactions: new structures and new conformational changes. Curr Opin Struct Biol 4: 857–867PubMedCrossRefGoogle Scholar
  11. 11.
    Batista FD & Harwood NE (2009) The who, how and where of antigen presentation to B cells. Nat Rev Immunol 9: 15–27PubMedCrossRefGoogle Scholar
  12. 12.
    Tolar PH, Joseph, Krueger, Peter D, Pierce, Susan K (2009) The Constant Region of the Membrane Immunoglobulin Mediates B Cell-Receptor Clustering and Signaling in Response to Membrane Antigens. Immunity doi:10.1016/j.immuni.2008.11.007Google Scholar
  13. 13.
    Tolar P, Sohn HW, Pierce SK (2005) The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer. Nat Immunol 6: 1168–1176PubMedCrossRefGoogle Scholar
  14. 14.
    Gil D, Schamel WW, Montoya M, et al (2002) Recruitment of Nck by CD3e reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation. Cell 109: 901–912PubMedCrossRefGoogle Scholar
  15. 15.
    Xu C, Gagnon E, Call ME, et al (2008) Regulation of T cell receptor activation by dynamic membrane binding of the CD3epsilon cytoplasmic tyrosine-based motif. Cell 135: 702–713PubMedCrossRefGoogle Scholar
  16. 16.
    Tolar P & Pierce SK (2009) A conformation-induced oligomerization model for B cell receptor microclustering and signaling. Curr Top Microbiol Immunol (in press)Google Scholar
  17. 17.
    Sohn HW, Tolar P, Pierce SK (2008) Membrane heterogeneities in the formation of B cell receptor-Lyn kinase microclusters and the immune synapse. J Cell Biol 182: 367–379PubMedCrossRefGoogle Scholar
  18. 18.
    Tolar P, Sohn HW, Pierce SK (2008) Viewing the antigen-induced initiation of B-cell activation in living cells. Immunol Rev 221: 64–76PubMedCrossRefGoogle Scholar
  19. 19.
    Corcos D (2007) Ligand-independent activity of the B cell antigen receptor in physiology and pathology. Arch Immunol Ther Exp (Warsz) 55: 77–82CrossRefGoogle Scholar
  20. 20.
    Corcos D, Dunda O, Butor C, et al (1995) Pre-B-cell development in the absence of lambda 5 in transgenic mice expressing a heavy-chain disease protein. Curr Biol 5: 1140–1148PubMedCrossRefGoogle Scholar
  21. 21.
    Corcos D, Iglesias A, Dunda O, et al (1991) Allelic exclusion in transgenic mice expressing a heavy chain disease-like human mu protein. Eur J Immunol 21: 2711–2716PubMedCrossRefGoogle Scholar
  22. 22.
    Shaffer AL & Schlissel MS (1997) A truncated heavy chain protein relieves the requirement for surrogate light chains in early B cell development. J Immunol 159: 1265–1275PubMedGoogle Scholar
  23. 23.
    Nimmerjahn F & Ravetch JV (2008) Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 8: 34–47PubMedCrossRefGoogle Scholar
  24. 24.
    Nimmerjahn F & Ravetch JV (2006) Fcgamma receptors: old friends and new family members. Immunity 24: 19–28PubMedCrossRefGoogle Scholar
  25. 25.
    Xiang Z, Cutler AJ, Brownlie RJ, et al (2007) FcgRIIb controls bone marrow plasma cell persistence and apoptosis. Nat Immunol 8: 419–429PubMedCrossRefGoogle Scholar
  26. 26.
    Bolland S & Ravetch JV (2000) Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity 13: 277–285PubMedCrossRefGoogle Scholar
  27. 27.
    Cohen S, Mc GI, Carrington S (1961) Gamma-globulin and acquired immunity to human malaria. Nature 192: 733–737PubMedCrossRefGoogle Scholar
  28. 28.
    Edozien JC, Gilles HM, Udeozo IOK (1962) Adult and cord-blood gamma-globulin and immunity to malaria in Nigerians. The Lancet 280: 951–955CrossRefGoogle Scholar
  29. 29.
    Crompton PD, Mircetic M, Weiss G, et al (2009) The TLR9 ligand CpG promotes the acquistion of Plasmodium falciparum-specific memory B cells in malaria-naive individuals. J Immunol (in press)Google Scholar
  30. 30.
    Moir S, Ho J, Malaspina A, et al (2008) Evidence for HIV-associated B-cell exhaustion in a dysfunctional memory B-cell compartment in HIV-infected viremic individuals. J Exp Med (in press)Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Susan K. Pierce
    • 1
  1. 1.Laboratory of ImmunogeneticsNational Institute of Allergy and Infectious Diseases, NIHRockvilleUSA

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