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 RIS Download
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