The molecular basis and biological significance of VH replacement

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

Research output: Contribution to journalReview article

37 Citations (Scopus)

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, 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
Volume197
DOIs
StatePublished - Jan 1 2004

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Genetic Recombination
B-Lymphoid Precursor Cells
B-Lymphocytes
Protein Sorting Signals
Genes
Immunoglobulin Genes
Transgenes
Base Pairing
Cell Differentiation
Nucleotides
Amino Acids
Cell Line
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The molecular basis and biological significance of VH replacement. / Zhang, Zhixin; Burrows, Peter D.; Cooper, Max D.

In: Immunological Reviews, Vol. 197, 01.01.2004, p. 231-242.

Research output: Contribution to journalReview article

Zhang, Zhixin ; Burrows, Peter D. ; Cooper, Max D. / The molecular basis and biological significance of VH replacement. In: Immunological Reviews. 2004 ; Vol. 197. pp. 231-242.
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