Somatic hypermutation does not require Rad54 and Rad54B-mediated homologous recombination
✍ Scribed by Linda Bross; Joanna Wesoly; Jean-Marie Buerstedde; Roland Kanaar; Heinz Jacobs
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 138 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Secondary diversification of immunoglobulin (Ig) genes occurs through somatic hypermutation (SHM) in B cells of the germinal center (GC). The GC reaction is associated with a high frequency ofDNA double‐strand breaks (DSB) in the hypermutation domain of Ig genes. Homologous recombination (HR) is a prominent DSB repair pathway. Among the proteins involved in HR are the Rad‐54 paralogues,Rad54 and Rad54B. To investigate whether Rad54/Rad54B‐mediated HR is involved in SHM, we determined the ratio of mutated versus non‐mutated Vλ PCR products from memory (IgM^–^, IgD^–^, Vλ1^+^) and GC (PNA^high^, Vλ1^+^) B cells, the mutation load, the mutation frequency, the base exchange pattern and the distribution of somatic mutations along the rearranged Vλ light chain (VλLC) genes. All these parameters of SHM were unaltered in memory and GC B cells lacking one or both Rad54 paralogues. Thus, our data indicate that Rad54 and Rad54B‐mediated HR is not essential for SHM. In addition, the finding that the ablation of RAD51 paralogues causes an increase in SHM argues against a direct involvement of HR in promoting SHM.