Advertisement

The Biology of IgE: The Generation of High-Affinity IgE Antibodies

  • Maria A. Curotto de LafailleEmail author
  • Juan J. Lafaille
Chapter

Abstract

B cells can undergo affinity maturation through the process of somatic hypermutation (SHM) followed by selection for high-affinity variants. Affinity maturation occurs in germinal centers (GC) and requires T–B cell cooperation. Extra GC B-cell responses are associated with the production of low-affinity antibodies. B cells producing high-affinity IgE during T-dependent responses are not directly selected in GC but are produced by the sequential switching of GC-selected high-affinity IgG-producing B cells. In contrast, natural low-affinity IgE can be generated without cognate T–B cell interactions in lymphopenic conditions. Low- and high-affinity IgE may differentially affect mast cell survival and degranulation and thus determine whether mast cells contribute to a beneficial or pathogenic environment.

Keywords

Germinal Center Affinity Maturation Sequential Switching Variant Peptide Germline Transcription 
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.

Notes

Acknowledgments

The Lafaille laboratory is supported by the NIH/NIAID, the National Multiple Sclerosis Society, the Strategic Program for Asthma Research, and the Crohn’s and Colitis Foundation of America.

References

  1. 1.
    K. D. McCoy, N. L. Harris, P. Diener, S. Hatak, B. Odermatt, L. Hangartner, B. M. Senn, B. J. Marsland, M. B. Geuking, H. Hengartner, A. J. Macpherson, R. M. Zinkernagel. Natural IgE production in the absence of MHC Class II cognate help. Immunity 24: 329–339, 2006.CrossRefPubMedGoogle Scholar
  2. 2.
    M. A. Curotto de Lafaille, S. Muriglan, M. J. Sunshine, Y. Lei, N. Kutchukhidze, G. C. Furtado, A. K. Wensky, D. Olivares-Villagomez, J. J. Lafaille. Hyper immunoglobulin E response in mice with monoclonal populations of B and T lymphocytes. J Exp Med 194: 1349–1359, 2001.CrossRefGoogle Scholar
  3. 3.
    C. Gonzalez-Espinosa, S. Odom, A. Olivera, J. P. Hobson, M. E. Martinez, A. Oliveira-Dos-Santos, L. Barra, S. Spiegel, J. M. Penninger, J. Rivera. Preferential signaling and induction of allergy-promoting lymphokines upon weak stimulation of the high affinity IgE receptor on mast cells. J Exp Med 197: 1453–1465, 2003.CrossRefPubMedGoogle Scholar
  4. 4.
    S. Yamasaki, E. Ishikawa, M. Kohno, T. Saito. The quantity and duration of FcRgamma signals determine mast cell degranulation and survival. Blood 103: 3093–3101, 2004.CrossRefPubMedGoogle Scholar
  5. 5.
    H. C. Oettgen, R. S. Geha. IgE regulation and roles in asthma pathogenesis. J Allergy Clin Immunol 107: 429–440, 2001.CrossRefPubMedGoogle Scholar
  6. 6.
    R. S. Geha, H. H. Jabara, S. R. Brodeur. The regulation of immunoglobulin E class-switch recombination. Nat Rev Immunol 3: 721–732, 2003.CrossRefPubMedGoogle Scholar
  7. 7.
    L. Xu, B. Gorham, S. C. Li, A. Bottaro, F. W. Alt, P. Rothman. Replacement of germ-line epsilon promoter by gene targeting alters control of immunoglobulin heavy chain class switching. Proc Natl Acad Sci USA 90: 3705–3709, 1993.CrossRefPubMedGoogle Scholar
  8. 8.
    L. Xu, P. Rothman. IFN-gamma represses epsilon germline transcription and subsequently down-regulates switch recombination to epsilon. Int Immunol 6: 515–521, 1994.CrossRefPubMedGoogle Scholar
  9. 9.
    M. Sugai, H. Gonda, T. Kusunoki, T. Katakai, Y. Yokota, A. Shimizu. Essential role of Id2 in negative regulation of IgE class switching. Nat Immunol 4: 25–30, 2003.CrossRefPubMedGoogle Scholar
  10. 10.
    J. P. Manis, M. Tian, F. W. Alt. Mechanism and control of class-switch recombination. Trends Immunol 23: 31–39, 2002.CrossRefPubMedGoogle Scholar
  11. 11.
    K. Kinoshita, T. Honjo. Linking class-switch recombination with somatic hypermutation. Nat Rev Mol Cell Biol 2: 493–503, 2001.CrossRefPubMedGoogle Scholar
  12. 12.
    J. A. Fenton, G. Pratt, A. C. Rawstron, G. J. Morgan. Isotype class switching and the pathogenesis of multiple myeloma. Hematol Oncol 20: 75–85, 2002.CrossRefPubMedGoogle Scholar
  13. 13.
    T. Yoshimoto, H. Okamura, Y. I. Tagawa, Y. Iwakura, K. Nakanishi. Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Proc Natl Acad Sci USA 94: 3948–3953, 1997.CrossRefPubMedGoogle Scholar
  14. 14.
    E. Severinson, C. Fernandez, J. Stavnezer. Induction of germ-line immunoglobulin heavy chain transcripts by mitogens and interleukins prior to switch recombination. Eur J Immunol 20: 1079–1084, 1990.CrossRefPubMedGoogle Scholar
  15. 15.
    N. Liu, N. Ohnishi, L. Ni, S. Akira, K. B. Bacon. CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells. Nat Immunol 4: 687–693, 2003.CrossRefPubMedGoogle Scholar
  16. 16.
    M. B. Harris, C. C. Chang, M. T. Berton, N. N. Danial, J. Zhang, D. Kuehner, B. H. Ye, M. Kvatyuk, P. P. Pandolfi, G. Cattoretti, R. Dalla-Favera, P. B. Rothman. Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching. Mol Cell Biol 19: 7264–7275, 1999.PubMedGoogle Scholar
  17. 17.
    G. Perona-Wright, K. Mohrs, J. Taylor, C. Zaph, D. Artis, E. J. Pearce, M. Mohrs. Cutting edge: Helminth infection induces IgE in the absence of mu- or delta-chain expression. J Immunol 181: 6697–6701, 2008.PubMedGoogle Scholar
  18. 18.
    Z. Orinska, A. Osiak, J. Lohler, E. Bulanova, V. Budagian, I. Horak, S. Bulfone-Paus. Novel B cell population producing functional IgG in the absence of membrane IgM expression. Eur J Immunol 32: 3472–3480, 2002.CrossRefPubMedGoogle Scholar
  19. 19.
    M. Hasan, B. Polic, M. Bralic, S. Jonjic, K. Rajewsky. Incomplete block of B cell development and immunoglobulin production in mice carrying the muMT mutation on the BALB/c background. Eur J Immunol 32: 3463–3471, 2002.CrossRefPubMedGoogle Scholar
  20. 20.
    K. Yoshida, M. Matsuoka, S. Usuda, A. Mori, K. Ishizaka, H. Sakano. Immunoglobulin switch circular DNA in the mouse infected with Nippostrongylus brasiliensis: evidence for successive class switching from mu to epsilon via gamma 1. Proc Natl Acad Sci USA 87: 7829–7833, 1990.CrossRefPubMedGoogle Scholar
  21. 21.
    F. C. Mills, G. Thyphronitis, F. D. Finkelman, E. E. Max. Ig mu-epsilon isotype switch in IL-4-treated human B lymphoblastoid cells. Evidence for a sequential switch. J Immunol 149: 1075–1085, 1992.PubMedGoogle Scholar
  22. 22.
    R. Mandler, F. D. Finkelman, A. D. Levine, C. M. Snapper. IL-4 induction of IgE class switching by lipopolysaccharide-activated murine B cells occurs predominantly through sequential switching. J Immunol 150: 407–418, 1993.PubMedGoogle Scholar
  23. 23.
    G. Siebenkotten, C. Esser, M. Wabl, A. Radbruch. The murine IgG1/IgE class switch program. Eur J Immunol 22: 1827–1834, 1992.CrossRefPubMedGoogle Scholar
  24. 24.
    H. H. Jabara, R. Loh, N. Ramesh, D. Vercelli, R. S. Geha. Sequential switching from mu to epsilon via gamma 4 in human B cells stimulated with IL-4 and hydrocortisone. J Immunol 151: 4528–4533, 1993.PubMedGoogle Scholar
  25. 25.
    F. C. Mills, M. P. Mitchell, N. Harindranath, E. E. Max. Human Ig S gamma regions and their participation in sequential switching to IgE. J Immunol 155: 3021–3036, 1995.PubMedGoogle Scholar
  26. 26.
    B. Baskin, K. B. Islam, B. Evengard, L. Emtestam, C. I. Smith. Direct and sequential switching from mu to epsilon in patients with Schistosoma mansoni infection and atopic dermatitis. Eur J Immunol 27: 130–135, 1997.CrossRefPubMedGoogle Scholar
  27. 27.
    K. Zhang, F. C. Mills, A. Saxon. Switch circles from IL-4-directed epsilon class switching from human B lymphocytes. Evidence for direct, sequential, and multiple step sequential switch from mu to epsilon Ig heavy chain gene. J Immunol 152: 3427–3435, 1994.PubMedGoogle Scholar
  28. 28.
    A. Erazo, N. Kutchukhidze, M. Leung, A. P. Christ, J. F. Urban, Jr., M. A. Curotto de Lafaille, J. J. Lafaille. Unique maturation program of the IgE response in vivo. Immunity 26: 191–203, 2007.CrossRefPubMedGoogle Scholar
  29. 29.
    I. M. Katona, J. F. Urban, Jr., F. D. Finkelman. The role of L3T4+ and Lyt-2+ T cells in the IgE response and immunity to Nippostrongylus brasiliensis. J Immunol 140: 3206–3211, 1988.PubMedGoogle Scholar
  30. 30.
    F. D. Finkelman, J. Holmes, I. M. Katona, J. F. Urban, Jr., M. P. Beckmann, L. S. Park, K. A. Schooley, R. L. Coffman, T. R. Mosmann, W. E. Paul. Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol 8: 303–333, 1990.CrossRefPubMedGoogle Scholar
  31. 31.
    S. Jung, G. Siebenkotten, A. Radbruch. Frequency of immunoglobulin E class switching is autonomously determined and independent of prior switching to other classes. J Exp Med 179: 2023–2026, 1994.CrossRefPubMedGoogle Scholar
  32. 32.
    C. G. Vinuesa, S. G. Tangye, B. Moser, C. R. Mackay. Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 5: 853–865, 2005.CrossRefPubMedGoogle Scholar
  33. 33.
    P. Schaerli, K. Willimann, A. B. Lang, M. Lipp, P. Loetscher, B. Moser. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 192: 1553–1562, 2000.CrossRefPubMedGoogle Scholar
  34. 34.
    D. Breitfeld, L. Ohl, E. Kremmer, J. Ellwart, F. Sallusto, M. Lipp, R. Forster. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192: 1545–1552, 2000.CrossRefPubMedGoogle Scholar
  35. 35.
    T. Chtanova, S. G. Tangye, R. Newton, N. Frank, M. R. Hodge, M. S. Rolph, C. R. Mackay. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol 173: 68–78, 2004.PubMedGoogle Scholar
  36. 36.
    A. U. Rasheed, H. P. Rahn, F. Sallusto, M. Lipp, G. Muller. Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells and is independent of CD57 expression. Eur J Immunol 36: 1892–1903, 2006.CrossRefPubMedGoogle Scholar
  37. 37.
    A. Suto, H. Nakajima, K. Hirose, K. Suzuki, S. Kagami, Y. Seto, A. Hoshimoto, Y. Saito, D. C. Foster, I. Iwamoto. Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line C(epsilon) transcription of IL-4-stimulated B cells. Blood 100: 4565–4573, 2002.CrossRefPubMedGoogle Scholar
  38. 38.
    K. Ozaki, R. Spolski, C. G. Feng, C. F. Qi, J. Cheng, A. Sher, H. C. Morse, 3rd, C. Liu, P. L. Schwartzberg, W. J. Leonard. A critical role for IL-21 in regulating immunoglobulin production. Science 298: 1630–1634, 2002.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Maria A. Curotto de Lafaille
    • 1
    Email author
  • Juan J. Lafaille
    • 1
  1. 1.Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute and Department of PathologyNew York University Scholl of MedicineNew YorkUSA

Personalised recommendations