Figure 1.

IgE class switch recombination, secreted, and membrane IgE (mIgE) transcripts. Top: mouse WT IgH locus is represented after VDJ recombination (not to scale). The recombined VDJ gene and constant (C) genes are represented as outlined boxes. I exons (I) and switch (S) regions preceding each constant gene (excepted Cδ) are represented as boxes and ovals, respectively. Black diamonds portray important regulatory elements: the intronic enhancer μ (Eμ), and the super-enhancer 3′ regulatory region (3′RR). Upper-middle: after B-cell activation, activation-induced deaminase (AID) is expressed and exerts its mutagenic activity on the VDJ gene, allowing production of antibodies with increased affinity for the Ag. AID is also targeted to S regions to initiate DNA double strand breaks, thereby inducing class switch recombination (CSR) between two S regions, here Sμ and Sγ1, or Sμ and Sε. This process allows the production of high-affinity IgG₁ antibodies, or low-affinity IgE. Lower-middle: cells can undergo more rounds of cell cycle or re-express AID after re-exposure to antigen and undergo a sequential CSR event, from γ1 to ε here, to produce high-affinity IgE antibodies. Bottom: IgE class-switched cells produce two main transcripts: mIgE transcripts including the four constant exons (CH1 to CH4), the two membrane (M1 and M2) anchor domains and unconventional polyadenylation (polyA) signals and/or secreted IgE transcripts, containing the constant genes and two conventional polyA signals. Alternate IgE transcripts have been described and could contribute to IgE response regulation.