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 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.
MeSH terms
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Animals
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Antibody-Producing Cells / immunology
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B-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / immunology
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Cells, Cultured
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Gene Targeting
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Genetic Diseases, X-Linked / immunology
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Humans
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Immunization
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Immunoglobulin E / biosynthesis*
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Immunoglobulin G / biosynthesis*
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Immunoglobulins / biosynthesis
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Immunologic Memory
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Interferon-gamma / biosynthesis
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Interleukin-21 Receptor alpha Subunit
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Interleukin-4 / biosynthesis
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Interleukin-4 / physiology
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Interleukins / physiology*
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Interleukin / genetics
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-21
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Severe Combined Immunodeficiency / immunology
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Signal Transduction
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T-Lymphocytes / immunology
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Toxoplasmosis, Animal / immunology
Substances
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IL21R protein, human
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Il21r protein, mouse
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Immunoglobulin G
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Immunoglobulins
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Interleukin-21 Receptor alpha Subunit
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Interleukins
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Receptors, Interleukin
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Receptors, Interleukin-21
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Interleukin-4
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Immunoglobulin E
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Interferon-gamma
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interleukin-21