A critical role for IL-21 in regulating immunoglobulin production.
Journal:
Science 2002 NovAuthors:
Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Sher A, Morse HC, Liu C, Schwartzberg PL, Leonard WJ
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
...[more] 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.[less]
Mesh Headings:
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