Top. The mouse IgH locus is represented after VDJ recombination (not to scale). The recombined VDJ gene and constant (C) genes are represented as outlined boxes. Horizontally-oriented ovals portray switch (S) regions (preceded by promoters and I exons, not shown) preceding each constant gene (excepted Cδ). Black ovals portray regulatory elements: intronic enhancer μ (Eμ), 3′ regulatory region (3′RR) and the newly identified lncRNA-CSR region, located approximately 2.6 mega-bases downstream of the 3′RR. The resulting immunoglobulin (Ig) protein is IgM, shown on the right.
Middle. After B cell activation, AID is expressed and induces its mutagenic activity on the VDJ gene, allowing production of IgM antibodies with increased affinity for the antigen. Then AID is targeted to S regions to initiate double strand breaks, thereby permitting recombination between two S regions, here Sμ and Sγ1. This process generates high affinity IgG1 antibodies and a diversified B cell repertoire.
Bottom. Cells can re-express AID after re-exposure to antigen and undergo a second class switch recombination event, from γ1 to ε here, to produce high affinity IgE antibodies (direct class switching from μ to ε is also possible). All these AID-mediated events shape the Ig repertoire to improve antigen affinity and to adapt the Ig class for an optimal immune response.