Fig. 1.

AID-independent and AID-dependent stages of B cell differentiation. Schematic diagram shows the Ig H chain locus. Rectangles and ovals represent V or C exons and switch regions. In the bone marrow, RAG-dependent V(D)J recombination selects one of each of the V, D, and J segments from respective gene pools and combines them into a single V(D)J exon (AID-independent and RAG-dependent stage of B cell differentiation). In peripheral lymphoid organs, the BCR is further diversified by SHM in an AID-dependent and RAG-independent fashion. SHM introduces mutations in the rearranged VDJ exon, yielding B cell submutants with diversified antigen specificities from which high affinity immunoglobulin producers are selected. CSR substitutes the upstream Cμ region with a downstream C_H region by deletion of the DNA intervening between Sμ and the downstream S region 5′ of the target C region. Deleted DNA is released as a “switch circle.” Like SHM, CSR is AID-dependent and RAG-independent.