Interleukin-21 stimulates B-cell immunoglobulin E synthesis in human beings concomitantly with activation-induced cytidine deaminase expression and differentiation into plasma cells
| Autor: | Kazunaga Agematsu, Hans D. Ochs, Shinji Kobayashi, Nagumo Haruo, Kazuo Sugane |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Transcriptional Activation X-Box Binding Protein 1 Cellular differentiation Plasma Cells Immunology Regulatory Factor X Transcription Factors In Vitro Techniques Biology Immunoglobulin E Interleukin 21 Cytidine Deaminase Activation-induced (cytidine) deaminase Humans Immunology and Allergy CD40 Antigens Interleukin 4 B-Lymphocytes Interleukins Receptors IgG Interleukin Cell Differentiation General Medicine Cytidine deaminase Middle Aged Molecular biology Interleukin-10 DNA-Binding Proteins Repressor Proteins Interleukin 10 biology.protein Female Interleukin-4 Positive Regulatory Domain I-Binding Factor 1 Transcription Factors |
| Zdroj: | Human Immunology. 70:35-40 |
| ISSN: | 0198-8859 |
| Popis: | Interleukin (IL)-21 downregulates immunoglobulin E (IgE) production in murine systems by inhibiting germline epsilon transcription in IL-4-stimulated B cells. We here sought to clarify the function of IL-21 in human B-cell IgE synthesis. IL-21 dramatically enhanced IgE production by human mononuclear cells, or purified total, naive, or memory B cells in the presence of IL-4 plus anti-CD40 mAb cross-linked with CD32-transfectants, and the production was strengthened with further addition of IL-10. It was concomitant to the enhancement of activation-induced cytidine deaminase (AID) mRNA expression, but no increase of germline epsilon transcription. We also observed that IL-21 promoted B-cell differentiation into plasma cells with increase of B-lymphocyte-induced maturation protein-1 (Blimp-1), but not X-box binding protein 1 (XBP-1), which was further accentuated by co-stimulation with IL-4 plus CD40 signaling. Thus, IL-21 is a strong inducer of IgE production in human beings concomitantly with AID expression and the differentiation into plasma cells. Our data suggest that IL-21 plays an important role in occurrence and the treatment of allergic disorders. |
| Databáze: | OpenAIRE |
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