The molecular basis and biological significance of VH replacement.

Academic Article

Abstract

  • First observed in mouse pre-B-cell lines and then in knock-in mice carrying self-reactive IgH transgenes, VH replacement has now been shown to contribute to the primary B-cell repertoire in humans. Through recombination-activating gene (RAG)-mediated recombination between a cryptic recombination signal sequence (RSS) present in almost all VH genes and the flanking 23 base pair RSS of an upstream VH gene, VH replacement renews the entire VH-coding region, while leaving behind a short stretch of nucleotides as a VH replacement footprint. In addition to extending the CDR3 region, the VH replacement footprints preferentially contribute charged amino acids. VH replacement rearrangement in immature B cells may either eliminate a self-reactive B-cell receptor or contribute to the generation of self-reactive antibodies. VH replacement may also rescue non-productive or dysfunctional VHDJH rearrangement in pro-B and pre-B cells. Conversely, VH replacement of a productive immunoglobulin H gene may generate non-productive VH replacement to disrupt or temporarily reverse the B-cell differentiation process. VH replacement can thus play a complex role in the generation of the primary B-cell repertoire.
  • Authors

    Published In

    Keywords

  • Animals, B-Lymphocytes, Cell Differentiation, Cell Line, Gene Expression Regulation, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Humans, Immunoglobulin Heavy Chains, Immunoglobulin Light Chains, Immunoglobulin Variable Region, Leukemia, Mice, Models, Immunological, Signal Transduction
  • Pubmed Id

  • 11940584
  • Authorlist

  • Zhang Z; Burrows PD; Cooper MD
  • Start Page

  • 231
  • End Page

  • 242
  • Volume

  • 197