Regulatory Mechanisms of Human Ige Synthesis
| Autor: | Yukiyoshi Yanagihara |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
biology
activation-induced cytidine deaminase General Medicine Cytidine deaminase Molecular biology Immunoglobulin class switching Transcription (biology) germline Cε transcription Second messenger system Activation-induced (cytidine) deaminase biology.protein STAT protein IgE isotype switching Immunology and Allergy switch recombination machinery Janus kinase Transcription factor adaptor molecule |
| Zdroj: | Allergology International. (1):1-12 |
| ISSN: | 1323-8930 |
| DOI: | 10.1046/j.1440-1592.2003.00275.x |
| Popis: | The induction of allergen-specific IgE synthesis requires the cognate interactions between B and T helper (Th) 2 cells. The B cell-activating signal for IgE synthesis is delivered through interleukin (IL)-4 or IL-13 and CD40 ligand, which are provided by activated Th2 cells. Signaling through the IL-4 receptor α chain (IL-4Rα) triggers IL-4- or IL-1 3-dependent germline Ce transcription by activating signal transducer and activator of transcription (STAT)-6 through members of the Janus kinase (JAK) family. In addition to the known JAK-STAT pathway, two adaptor molecules associated with the IL-4Rα, which include Src homologous and collagen (Shc) and a product of the fes proto-oncogene family, are involved in the induction of germline Ce transcription. These adaptor molecules transmit the downstream signaling, leading to activation of PU.1, a product of the ets proto-oncogene family, which cooperates functionally with STAT-6 for germline Ce transcription. Ligation of CD40 in the presence of IL-4 or IL-13 leads to expression of activation-induced cytidine deaminase (AID). This novel RNA-editing enzyme plays a role upstream of the putative switch recombinase, activation of which results in IgE isotype switching, mature Ce transcription and IgE synthesis. Although CD40 signaling activates multiple pathways that are critical for the activation of the switch recombination machinery, none of the known second messengers and transcription factors generated by CD40 ligation is involved in AID expression and isotype switching. Elucidation of the merging point of IL-4Rα and CD40 signaling pathways required for IgE switching will provide potential new strategies for the isotype-specific regulation of IgE synthesis. |
| Databáze: | OpenAIRE |
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