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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1784-1793. Prepublished online as a Blood First Edition Paper on June 25, 2008; DOI 10.1182/blood-2008-02-142745. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-142745v1 112/5/1784    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Avery, D. T. Articles by Tangye, S. G. Search for Related Content PubMed PubMed Citation Articles by Avery, D. T. Articles by Tangye, S. G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY STAT3 is required for IL-21–induced secretion of IgE from human naive B cells Danielle T. Avery1, Cindy S. Ma1, Vanessa L. Bryant1, Brigitte Santner-Nanan2, Ralph Nanan2, Melanie Wong3, David A. Fulcher4, Matthew C. Cook5, and Stuart G. Tangye1 1 Immunology and Inflammation Group, Garvan Institute of Medical Research, Darlinghurst; 2 Discipline of Paediatrics, Nepean Clinical School, University of Sydney, Penrith; 3 Department of Immunology and Allergy, Children's Hospital, Westmead; 4 Immunology Unit, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead; and 5 Department of Immunology, Canberra Hospital, Woden, Australia The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced by the fact that it comprises less than 0.0001% of serum Ig, and aberrant production causes atopic conditions, including allergy, rhinitis, and anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human and murine B cells, whereas interferon- can antagonize this effect. IL-21 has also been recognized for its ability to suppress IL-4–induced IgE production by murine B cells. Here, we identified IL-21 as an inducer of IgE production by CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B cells, such that the levels detected under these conditions exceeded those induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations revealed that the ability of IL-21 to induce IgE secretion, and augment that driven by IL-4, was STAT3-dependent. These findings highlight a fundamental difference between the regulation of IgE production by human and murine B cells and have implications for the dysregulated production of IgE in conditions characterized by extremely high levels of serum IgE. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. C. Cook and S. G. Tangye Primary immune deficiencies affecting lymphocyte differentiation: lessons from the spectrum of resulting infections Int. Immunol., September 1, 2009; 21(9): 1003 - 1011. [Abstract] [Full Text] [PDF] G. Heine, A. Dahten, K. Hilt, D. Ernst, M. Milovanovic, B. Hartmann, and M. Worm Liver X Receptors Control IgE Expression in B Cells J. Immunol., May 1, 2009; 182(9): 5276 - 5282. [Abstract] [Full Text] [PDF] Y. Minegishi and H. Karasuyama Defects in Jak-STAT-mediated cytokine signals cause hyper-IgE syndrome: lessons from a primary immunodeficiency Int. Immunol., February 1, 2009; 21(2): 105 - 112. [Abstract] [Full Text] [PDF] S. G. Tangye, M. C. Cook, and D. A. Fulcher Insights into the Role of STAT3 in Human Lymphocyte Differentiation as Revealed by the Hyper-IgE Syndrome J. Immunol., January 1, 2009; 182(1): 21 - 28. [Abstract] [Full Text] [PDF]

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