isotype switching to IgE isotypes

Definition

Target type: biologicalprocess

The switching of activated B cells from IgM biosynthesis to IgE biosynthesis, accomplished through a recombination process involving an intrachromosomal deletion between switch regions that reside 5' of the IgM and IgE constant region gene segments in the immunoglobulin heavy chain locus. [ISBN:0781735149, PMID:12370374, PMID:2113175, PMID:9186655]

Isotype switching to IgE is a complex biological process that occurs in B cells during their differentiation into plasma cells. It involves a switch in the constant region of the antibody heavy chain, resulting in the production of IgE antibodies.

**1. Activation of B Cells:**
B cells are activated by encountering an antigen, which binds to the B cell receptor (BCR). This activation triggers a cascade of signaling events that lead to B cell proliferation and differentiation.

**2. T Cell Help:**
Activated B cells require help from T helper cells (Th2 cells) to undergo isotype switching. Th2 cells release cytokines, including interleukin-4 (IL-4), which induce the expression of specific transcription factors in B cells.

**3. Transcription Factors:**
The cytokines released by Th2 cells activate transcription factors such as STAT6 and NF-κB, which bind to specific DNA sequences in the immunoglobulin heavy chain locus.

**4. DNA Recombination:**
The activated transcription factors initiate a process called class switch recombination (CSR) within the immunoglobulin heavy chain locus. This process involves a series of DNA double-strand breaks and rejoining events.

**5. Switching to the IgE Locus:**
The CSR mechanism specifically targets the switch region upstream of the IgE constant region (Cε). This region contains repetitive DNA sequences that are specifically recognized by the AID (activation-induced cytidine deaminase) enzyme.

**6. AID-Mediated DNA Damage:**
AID acts on the switch regions, causing DNA damage and initiating DNA repair processes.

**7. DNA Repair and Recombination:**
The DNA damage and repair processes lead to a recombination event that joins the VDJ region of the antibody gene with the IgE constant region.

**8. Expression of IgE:**
After successful recombination, the B cell now expresses the IgE heavy chain. This newly synthesized IgE heavy chain combines with the light chain to form a complete IgE antibody.

**9. Plasma Cell Differentiation:**
The B cell further differentiates into a plasma cell, a specialized cell dedicated to producing and secreting large amounts of IgE antibodies.

**10. IgE Function:**
IgE antibodies bind to high-affinity receptors (FcεRI) on mast cells and basophils. When IgE encounters its specific antigen, it triggers the degranulation of these cells, releasing histamine and other inflammatory mediators. This process is involved in allergic reactions and defense against parasitic infections.**
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Proteins (2)

Compounds (4)