Molecular regulation of human IgE synthesis
Human IgE synthesis is largely dependent on the production of interleukin (IL)-4 or IL-13 and the expression of CD40 ligand. Such B cell help is not only provided by CD4+ T cells, but also by CD8+ T cells, γδ T cells, mast cells, basophils and eosinophils. The IL-4 receptor a chain (IL-4Ra) expresse...
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| Format: | Article |
| Language: | English |
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Elsevier
1999-01-01
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| Series: | Allergology International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893015314751 |
| _version_ | 1818848930457190400 |
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| author | Yukiyoshi Yanagihara |
| author_facet | Yukiyoshi Yanagihara |
| author_sort | Yukiyoshi Yanagihara |
| collection | DOAJ |
| description | Human IgE synthesis is largely dependent on the production of interleukin (IL)-4 or IL-13 and the expression of CD40 ligand. Such B cell help is not only provided by CD4+ T cells, but also by CD8+ T cells, γδ T cells, mast cells, basophils and eosinophils. The IL-4 receptor a chain (IL-4Ra) expressed on B cells is shared by the functional IL-4R and IL-13R and is a crucial component required for signal transduction leading to germline Ce transcription, which is a prerequisite for IgE isotype switching. Interleukin-4 activates Janus kinase (JAK)1, JAK3 and phosphatidylinositol 3-kinase (PI3-K) and, subsequently, induces nuclear translocation of signal transducers and activators of transcription (STAT)6 and nuclear factor (NF)-kB, which interact at the level of the Iε promoter. The two variants of the IL-4Rα, which have been identified in association with atopy, are associated with enhanced responsiveness to IL-4. Ligation of CD40 on B cells up-regulates IL-4- or IL-13-driven germline Cε transcription and further induces deletional switch recombination that results in IgE isotype switching, mature Cε transcription and IgE synthesis. Signaling pathways mediated by CD40 include activation of Lyn, PI3-K, JAK3 and members of the mitogen-activated protein kinase subfamily, multimerization of tumor necrosis factor-a receptor-associated factor (TRAF)2, TRAF3, TRAF5 and TRAF6 and translocation of NF-kB and STAT3. In addition, Ku70/86, DNA-dependent protein kinase and rad51/54 may be involved in switch recombination. Taken together, activation of kinases, induction of second messengers, nuclear expression of transcription factors and localization of DNA-binding proteins are integrated to produce the terminal differentiation of a B cell into an IgE-secreting plasma cell. Elucidation of the detailed mechanisms of IgE isotype switching will contribute to the development of potential new therapeutic procedures for the regulation of the IgE response in atopic patients. |
| first_indexed | 2024-12-19T06:25:10Z |
| format | Article |
| id | doaj.art-88bfc6e6be9f4adb922b3424fea407cb |
| institution | Directory Open Access Journal |
| issn | 1323-8930 |
| language | English |
| last_indexed | 2024-12-19T06:25:10Z |
| publishDate | 1999-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Allergology International |
| spelling | doaj.art-88bfc6e6be9f4adb922b3424fea407cb2022-12-21T20:32:35ZengElsevierAllergology International1323-89301999-01-0148211111910.1046/j.1440-1592.1999.00124.xMolecular regulation of human IgE synthesisYukiyoshi YanagiharaHuman IgE synthesis is largely dependent on the production of interleukin (IL)-4 or IL-13 and the expression of CD40 ligand. Such B cell help is not only provided by CD4+ T cells, but also by CD8+ T cells, γδ T cells, mast cells, basophils and eosinophils. The IL-4 receptor a chain (IL-4Ra) expressed on B cells is shared by the functional IL-4R and IL-13R and is a crucial component required for signal transduction leading to germline Ce transcription, which is a prerequisite for IgE isotype switching. Interleukin-4 activates Janus kinase (JAK)1, JAK3 and phosphatidylinositol 3-kinase (PI3-K) and, subsequently, induces nuclear translocation of signal transducers and activators of transcription (STAT)6 and nuclear factor (NF)-kB, which interact at the level of the Iε promoter. The two variants of the IL-4Rα, which have been identified in association with atopy, are associated with enhanced responsiveness to IL-4. Ligation of CD40 on B cells up-regulates IL-4- or IL-13-driven germline Cε transcription and further induces deletional switch recombination that results in IgE isotype switching, mature Cε transcription and IgE synthesis. Signaling pathways mediated by CD40 include activation of Lyn, PI3-K, JAK3 and members of the mitogen-activated protein kinase subfamily, multimerization of tumor necrosis factor-a receptor-associated factor (TRAF)2, TRAF3, TRAF5 and TRAF6 and translocation of NF-kB and STAT3. In addition, Ku70/86, DNA-dependent protein kinase and rad51/54 may be involved in switch recombination. Taken together, activation of kinases, induction of second messengers, nuclear expression of transcription factors and localization of DNA-binding proteins are integrated to produce the terminal differentiation of a B cell into an IgE-secreting plasma cell. Elucidation of the detailed mechanisms of IgE isotype switching will contribute to the development of potential new therapeutic procedures for the regulation of the IgE response in atopic patients.http://www.sciencedirect.com/science/article/pii/S1323893015314751atopyCD40 ligandIgEinterleukin-4switch recombination |
| spellingShingle | Yukiyoshi Yanagihara Molecular regulation of human IgE synthesis Allergology International atopy CD40 ligand IgE interleukin-4 switch recombination |
| title | Molecular regulation of human IgE synthesis |
| title_full | Molecular regulation of human IgE synthesis |
| title_fullStr | Molecular regulation of human IgE synthesis |
| title_full_unstemmed | Molecular regulation of human IgE synthesis |
| title_short | Molecular regulation of human IgE synthesis |
| title_sort | molecular regulation of human ige synthesis |
| topic | atopy CD40 ligand IgE interleukin-4 switch recombination |
| url | http://www.sciencedirect.com/science/article/pii/S1323893015314751 |
| work_keys_str_mv | AT yukiyoshiyanagihara molecularregulationofhumanigesynthesis |