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A Critical Role for IL-21 in Regulating Immunoglobulin Production

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

A Critical Role for IL-21 in Regulating Immunoglobulin Production

  1. Katsutoshi Ozaki1,*,
  2. Rosanne Spolski1,
  3. Carl G. Feng2,
  4. Chen-Feng Qi3,
  5. Jun Cheng4,
  6. Alan Sher2,
  7. Herbert C. Morse III3,
  8. Chengyu Liu5,
  9. Pamela L. Schwartzberg4,
  10. Warren J. Leonard1,
  1. 1 Laboratory of Molecular Immunology,
  2. 5 Transgenic Facility, National Heart, Lung, and Blood Institute,
  3. 2 Laboratory of Parasitic Disease,
  4. 3 Laboratory of Immunopathology, National Institute of Allergy and Infectious Disease,
  5. 4 Genetic Disease Research Branch, National Human Genome Research Institute, Building 49, Room 4A38, National Institutes of Health, Bethesda, MD 20892–1674, USA.


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}

  • Received for publication 5 August 2002.
  • Accepted for publication 30 September 2002.


K. Ozaki, R. Spolski, C. G. Feng, C.-F. Qi, J. Cheng, A. Sher, H. C. Morse, C. Liu, P. L. Schwartzberg, and W. J. Leonard, A Critical Role for IL-21 in Regulating Immunoglobulin Production. Science 298, 1630-1634 (2002).

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