The molecular basis and biological significance of VH replacement
Article first published online: 6 JAN 2004
Volume 197, Issue 1, pages 231–242, January 2004
How to Cite
Zhang, Z., Burrows, P. D. and Cooper, M. D. (2004), The molecular basis and biological significance of VH replacement. Immunological Reviews, 197: 231–242. doi: 10.1111/j.0105-2896.2004.0107.x
- Issue published online: 6 JAN 2004
- Article first published online: 6 JAN 2004
Summary: 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.