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A Critical Role for IL-21 in Regulating Immunoglobulin Production

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Science  22 Nov 2002:
Vol. 298, Issue 5598, pp. 1630-1634
DOI: 10.1126/science.1077002

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Abstract

The cytokine interleukin-21 (IL-21) is closely related to IL-2 and IL-15, and their receptors all share the common cytokine receptor γ chain, γc, 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 γc-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID.

  • * Present address: Institute of Medical Science, University of Tokyo, Tokyo, Japan.

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

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