title: Biased distribution of recombination sites within S regions upon immunoglobulin class switch recombination induced by transforming growth factor beta and lipopolysaccharide.
abstract: 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.
authors.affiliation: Department of Biophysics, Faculty of Science, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwasato
authors.forename: H
authors.initials: H
authors.lastname: Arakawa
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Honjo
authors.forename: H
authors.initials: H
authors.lastname: Yamagishi
mesh_terms: D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004270:DNA, Circular / Q000235:genetics; D005260:Female; D015723:Gene Library; D005812:Genes, Switch / Q000187:drug effects; D007074:Immunoglobulin G / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000187:drug effects; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D011995:Recombination, Genetic / Q000187:drug effects; D015183:Restriction Mapping; D013154:Spleen / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D004270:DNA, Circular; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D016212:Transforming Growth Factor beta; D015847:Interleukin-4