Schematic representation of antibody maturation. The V region is followed by constant region genes: IGHM, IGHG3, IGHG1, IGHA1, IGHG2, IGHG4, IGHGE, and IGHA2, each having an intronic (I) promoter (not shown), a repetitive non-coding switch (S) region (ovals) and the constant (C) region exons (rectangles). Regulatory elements include individual enhancers (Eu and Edelta), two super-enhancers (3' regulatory regions 1 and 2; 3'RR1 and 3'RR2), each followed by CTCF-binding elements (3'CBE1 and 3'CBE2). B cell activation leads to expression of AID and non-coding transcription from the IGHM promoter and one or more downstream promoters (IGHG1 here). AID acts co-transcriptionally to initiate somatic hypermutation (SHM) at the V region and the transcribed donor Smu and acceptor Sgamma1 S regions. Processing of AID-induced mismatches in S regions creates double-strand breaks that are ligated via class switch recombination (CSR). This results in the exchange of constant regions (Cmu for Cgamma1) yielding a new antibody isotype, IgG1.
