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A critical role for IL-21 in regulating immunoglobulin production.

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, gammac, 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 gammac-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID.

Pubmed ID: 12446913

Authors

  • Ozaki K
  • Spolski R
  • Feng CG
  • Qi CF
  • Cheng J
  • Sher A
  • Morse HC
  • Liu C
  • Schwartzberg PL
  • Leonard WJ

Journal

Science (New York, N.Y.)

Publication Data

November 22, 2002

Associated Grants

None

Mesh Terms

  • Animals
  • Antibody-Producing Cells
  • B-Lymphocytes
  • CD4-Positive T-Lymphocytes
  • Cells, Cultured
  • Gene Targeting
  • Genetic Diseases, X-Linked
  • Humans
  • Immunization
  • Immunoglobulin E
  • Immunoglobulin G
  • Immunoglobulins
  • Immunologic Memory
  • Interferon-gamma
  • Interleukin-21 Receptor alpha Subunit
  • Interleukin-4
  • Interleukins
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin
  • Receptors, Interleukin-21
  • Severe Combined Immunodeficiency
  • Signal Transduction
  • T-Lymphocytes
  • Toxoplasmosis, Animal