R-loops at Immunoglobulin Class Switch Regions in the Chromosomes of Stimulated B Cells

Nat Immunol. 2003 May;4(5):442-51. doi: 10.1038/ni919.

Abstract

The mechanism responsible for immunoglobulin class switch recombination is unknown. Previous work has shown that class switch sequences have the unusual property of forming RNA-DNA hybrids when transcribed in vitro. Here we show that the RNA-DNA hybrid structure that forms in vitro is an R-loop with a displaced guanine (G)-rich strand that is single-stranded. This R-loop structure exists in vivo in B cells that have been stimulated to transcribe the gamma3 or the gamma2b switch region. The length of the R-loops can exceed 1 kilobase. We propose that this distinctive DNA structure is important in the class switch recombination mechanism

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Base Composition
  • Chromosomes, Human / genetics
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / genetics
  • Humans
  • Immunoglobulin Switch Region*
  • In Vitro Techniques
  • Mice
  • Models, Genetic
  • Models, Immunological
  • Nucleic Acid Conformation
  • RNA / chemistry
  • RNA / genetics
  • Recombination, Genetic
  • Transcription, Genetic

Substances

  • DNA, Single-Stranded
  • RNA