positive regulation of isotype switching to IgE isotypes

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of isotype switching to IgE isotypes. [GOC:jid]

Positive regulation of isotype switching to IgE isotypes is a complex process involving multiple factors and signaling pathways. It begins with the activation of B cells by antigen and T cell-derived signals, such as CD40 ligand (CD40L) and cytokines, primarily interleukin-4 (IL-4) and interleukin-13 (IL-13). These signals activate transcription factors like STAT6 and NF-κB, which induce the expression of germline transcripts (GLTs) specific for the IgE constant region (Cε). GLTs are unspliced RNA molecules that contain the coding sequence for the Cε region and are transcribed from the IgE locus. The presence of GLTs promotes the recruitment of the enzyme activation-induced cytidine deaminase (AID) to the switch region upstream of the Cε gene. AID catalyzes the deamination of cytosine bases to uracil within the switch region, leading to DNA double-strand breaks. This DNA damage triggers a process called class switch recombination (CSR), where the switch region upstream of the Cμ gene (encoding IgM) is recombined with the switch region upstream of the Cε gene. The result is a DNA rearrangement that deletes the Cμ gene and brings the Cε gene into proximity with the variable region, enabling the production of IgE antibodies. This process is tightly regulated by several factors, including the presence of specific transcription factors, epigenetic modifications, and the availability of DNA repair machinery. Notably, IL-4 and IL-13 not only activate STAT6 and NF-κB but also suppress the transcription of GLTs for other isotypes, ensuring the preferential switching to IgE. In addition, the presence of the transcription factor IRF4 further enhances the expression of IgE-specific GLTs and promotes CSR to IgE. Overall, positive regulation of isotype switching to IgE is a multi-step process involving complex interactions between various factors, ultimately leading to the production of IgE antibodies, which are important mediators of allergic reactions and other immune responses.'
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Proteins (1)

Compounds (1)