The molecular basis and biological significance of VH replacement

Zhixin Zhang, Peter D. Burrows, Max D. Cooper

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations


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, V H 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. V H 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. V H replacement can thus play a complex role in the generation of the primary B-cell repertoire.

Original languageEnglish (US)
Pages (from-to)231-242
Number of pages12
JournalImmunological Reviews
StatePublished - Jan 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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