Schematic diagram ofIGHgene rearrangement, CSR, and SHM during B-cell development. D_H to J_H recombination occurs at the pro-B stage, producing an incomplete DJ_H rearrangement. This is followed by V_H to DJ_H recombination at the pre-B stage that will give rise to a complete VDJ_H rearrangement. If this VDJ_H is functional, the cell will develop into a mature B-cell–expressing surface IgM (IgM⁺). These cells can enter the GCs where SHM and CSR occur, thus becoming VH-mutated, class-switched (eg, IgA) memory B or plasma cells. Circles preceding the C_H gene segments (except δ) represent the switch regions. Dotted lines on the V_H, D_H, and J_H segments and the variable region of the Ig protein represent hypermutated genes after the SHM process.