BIASED DISTRIBUTION OF RECOMBINATION SITES WITHIN S-REGIONS UPON IMMUNOGLOBULIN CLASS SWITCH RECOMBINATION INDUCED BY TRANSFORMING GROWTH-FACTOR-BETA AND LIPOPOLYSACCHARIDE

We have characterized extrachromosomal circular DNAs from adult mouse spleen cells that were induced to switch to immunoglobulin A (IgA) with bacterial lipopolysaccharide (LPS) and transforming growth factor-beta (TGF-beta), and identified breakpoints of S-mu/S-gamma-3, S-mu/S-gamma-2, S-mu/S-alpha, S-gamma-3/S-alpha, and S-gamma-2/S-alpha recombinants. The S-mu recombination donor sites clustered in the 3' half of the S-mu region, while the S-alpha recombination acceptor sites clustered in the 5' half of the S-alpha region. In addition, donor and acceptor sites of S-gamma regions also clustered in the 3' and 5' parts, respectively. These site preferences are in sharp contrast to the dispersed distribution of S-mu/S-gamma-1 breakpoints within both S-mu and S-gamma-1 regions upon IgG1 switch induced by LPS and interleukin 4. Our results support the hypotheses that TGF-beta increases the frequency of switch recombination events to IgA and that the switch recombination to IgA often proceeds by successive recombination of S-mu/S-gamma and S-gamma/S-alpha.