A Critical Role for IL-21 in Regulating Immunoglobulin Production
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, γ 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 γ c -dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID.
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- Authors
- Ozaki, K., Spolski, R., Feng, C. G., Qi, C.-F., Cheng, J., Sher, A., Morse, H. C., Liu, C., Schwartzberg, P. L., & Leonard, W. J.
- Affiliations
- Laboratory of Molecular Immunology,
- Laboratory of Parasitic Disease,
- National Institute of Allergy and Infectious Diseases (US)
- National Institutes of Health (US)
- National Heart, Lung, and Blood Institute (US)
- Corresponding author
- Ozaki, Katsutoshi
- Leonard, Warren J.
- ORCID
- Venue
- Science
- Published
- 2002-11-22
- Volume
- 298
- Issue
- 5598
- Pages
- 1630-1634
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1985577573
- Cited by
- 978
- References
- 0
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 25 · 2023: 26 · 2022: 24 · 2021: 40 · 2020: 39 · 2019: 38 · 2018: 44 · 2017: 35 · 2016: 57 · 2015: 48 · 2014: 43 · 2013: 69 · 2012: 61
- FWCI
- 8.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-21, IL-21 receptor, antibody production, IgE, IgG1, dysgammaglobulinemia, IL-4, B cell function, gamma chain cytokines, X-linked severe combined immunodeficiency, interleukin-2, IL-15, lymphoid development
- MeSH terms
- Interleukin-21, Animals, Antibody-Producing Cells, B-Lymphocytes, Cells, Cultured, Humans, Immunoglobulin E, Immunoglobulin G, Immunization, Immunoglobulins, Immunologic Memory, Interferon-gamma, Interleukins, Lymphocyte Activation, Mice, Inbred C57BL, T-Lymphocytes, Toxoplasmosis, Animal, Signal Transduction, CD4-Positive T-Lymphocytes, Interleukin-4, Severe Combined Immunodeficiency, Receptors, Interleukin, Mice, Knockout, Gene Targeting, Genetic Diseases, X-Linked, Mice, Receptors, Interleukin-21, Interleukin-21 Receptor alpha Subunit
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