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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-04-1115.

Submitted April 19, 2002
Accepted July 20, 2002
Interleukin-21 prevents antigen-induced IgE production by inhibiting germline C transcription of IL-4-stimulated B cells
Akira Suto, Hiroshi Nakajima*, Koichi Hirose, Kotaro Suzuki, Shin-ichiro Kagami, Yohei Seto, Aihiro Hoshimoto, Yasushi Saito, Donald C Foster, and Itsuo Iwamoto
Internal Medicine II, Chiba University School of Medicine, Chiba, Japan
Cytokine Biology, ZymoGenetics Inc., Seattle, WA, USA
* Corresponding author; email: nakajimh{at}intmed02.m.chiba-u.ac.jp.
Interleukin-21 (IL-21) has recently been identified as a multi-functional cytokine that induces the proliferation of T cells and B cells and differentiation of natural killer cells. To determine whether IL-21 regulates IL-4-mediated immune responses, we examined the effect of IL-21 on antigen-specific IgE production in mice. We also examined the effect of IL-21 on IL-4-induced IgE production from B cells and antigen-induced T helper 2 (Th2) cell differentiation. The in vivo injection of IL-21 prevented antigen-specific IgE but not IgG2a production upon immunization. IL-21 did not affect Th2 cell differentiation or IL-4 production from CD4+ T cells but directly inhibited IL-4-induced IgE production from B cells at single cell levels. Moreover, IL-21 inhibited IL-4-induced germline C transcription in B cells without the inhibition of Stat6 activation. Taken together, these results indicate that IL-21 downregulates IgE production from IL-4-stimulated B cells through the inhibition of germline C transcription and thus suggest that IL-21 may be useful for the treatment of IgE-dependent allergic diseases.

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