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.
Ozaki
Katsutoshi
K
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA.
Spolski
Rosanne
R
Feng
Carl G
CG
Qi
Chen-Feng
CF
Cheng
Jun
J
Sher
Alan
A
Morse
Herbert C
HC
Liu
Chengyu
C
Schwartzberg
Pamela L
PL
Leonard
Warren J
WJ
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018390:Gene Targeting; D040181:Genetic Diseases, X-Linked / Q000276:immunology; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007136:Immunoglobulins / Q000096:biosynthesis; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D053738:Interleukin-21 Receptor alpha Subunit; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053655:Receptors, Interleukin-21; D016511:Severe Combined Immunodeficiency / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology; D000098546:Interleukin-21
C508117:IL21R protein, human; C508118:Il21r protein, mouse; D007074:Immunoglobulin G; D007136:Immunoglobulins; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D000098546:Interleukin-21