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Science 22 November 2002:
Vol. 298. no. 5598, pp. 1630 - 1634
DOI: 10.1126/science.1077002
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Reports

A Critical Role for IL-21 in Regulating Immunoglobulin Production

Katsutoshi Ozaki,1* Rosanne Spolski,1 Carl G. Feng,2 Chen-Feng Qi,3 Jun Cheng,4 Alan Sher,2 Herbert C. Morse III,3 Chengyu Liu,5 Pamela L. Schwartzberg,4 Warren J. Leonard1dagger

The cytokine interleukin-21 (IL-21) is closely related to IL-2 and IL-15, and their receptors all share the common cytokine receptor gamma  chain, gamma c, which is mutated in humans with X-linked severe combined immunodeficiency disease (XSCID). We demonstrate that, although mice deficient in the receptor for IL-21 (IL-21R) have normal lymphoid development, after immunization, these animals have higher production of the immunoglobulin IgE, but lower IgG1, than wild-type animals. Mice lacking both IL-4 and IL-21R exhibited a significantly more pronounced phenotype, with dysgammaglobulinemia, characterized primarily by a severely impaired IgG response. Thus, IL-21 has a significant influence on the regulation of B cell function in vivo and cooperates with IL-4. This suggests that these gamma c-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID.

1 Laboratory of Molecular Immunology,
5 Transgenic Facility, National Heart, Lung, and Blood Institute,
2 Laboratory of Parasitic Disease,
3 Laboratory of Immunopathology, National Institute of Allergy and Infectious Disease,
4 Genetic Disease Research Branch, National Human Genome Research Institute, Building 49, Room 4A38, National Institutes of Health, Bethesda, MD 20892-1674, USA.
*   Present address: Institute of Medical Science, University of Tokyo, Tokyo, Japan.

dagger    To whom correspondence should be addressed. E-mail: wjl{at}helix.nih.gov

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Cancer Res. 63, 9016-9022
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Science 302, 875-878
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IL-21 Activates Both Innate and Adaptive Immunity to Generate Potent Antitumor Responses that Require Perforin but Are Independent of IFN-{gamma}.
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J. Immunol. 171, 608-615
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