title: Interleukin-21 stimulates B-cell immunoglobulin E synthesis in human beings concomitantly with activation-induced cytidine deaminase expression and differentiation into plasma cells.
abstract: 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.
authors.affiliation: Department of Infection and Host Defense, Shinshu University, Matsumoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Nagumo
authors.initials: N
authors.lastname: Haruo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugane
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Kazunaga
authors.initials: K
authors.lastname: Agematsu
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation; D003564:Cytidine Deaminase / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017452:Receptors, IgG / Q000276:immunology; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D015533:Transcriptional Activation / Q000276:immunology; D000071717:X-Box Binding Protein 1; D000098546:Interleukin-21
chemical_list: D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D007378:Interleukins; D017452:Receptors, IgG; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D016753:Interleukin-10; C087042:PRDM1 protein, human; D015847:Interleukin-4; D007073:Immunoglobulin E; D000074462:Positive Regulatory Domain I-Binding Factor 1; D003564:Cytidine Deaminase; D000098546:Interleukin-21