Publication Date:
2002-11-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ozaki, Katsutoshi -- Spolski, Rosanne -- Feng, Carl G -- Qi, Chen-Feng -- Cheng, Jun -- Sher, Alan -- Morse, Herbert C 3rd -- Liu, Chengyu -- Schwartzberg, Pamela L -- Leonard, Warren J -- New York, N.Y. -- Science. 2002 Nov 22;298(5598):1630-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12446913" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibody-Producing Cells/immunology
;
B-Lymphocytes/*immunology
;
CD4-Positive T-Lymphocytes/immunology
;
Cells, Cultured
;
Gene Targeting
;
Genetic Diseases, X-Linked/immunology
;
Humans
;
Immunization
;
Immunoglobulin E/*biosynthesis
;
Immunoglobulin G/*biosynthesis
;
Immunoglobulins/biosynthesis
;
Immunologic Memory
;
Interferon-gamma/biosynthesis
;
Interleukin-21 Receptor alpha Subunit
;
Interleukin-4/biosynthesis/physiology
;
Interleukins/*physiology
;
Lymphocyte Activation
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Receptors, Interleukin/genetics/metabolism
;
Receptors, Interleukin-21
;
Severe Combined Immunodeficiency/immunology
;
Signal Transduction
;
T-Lymphocytes/immunology
;
Toxoplasmosis, Animal/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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