| First Author | Guikema JE | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 12 | Pages | 8450-9 |
| PubMed ID | 19050263 | Mgi Jnum | J:142067 |
| Mgi Id | MGI:3820355 | Doi | 10.4049/jimmunol.181.12.8450 |
| Citation | Guikema JE, et al. (2008) Reassessment of the role of Mut S homolog 5 in Ig class switch recombination shows lack of involvement in cis- and trans-switching. J Immunol 181(12):8450-9 |
| abstractText | When B cells are activated after immunization or infection, they exchange the gene encoding the Ig H chain C region by class switch recombination (CSR). CSR generally occurs by an intrachromosomal deletional recombination within switch (S) region sequences. However, approximately 10% of CSR events occur between chromosome homologs (trans- or interallele CSR), suggesting that the homologous chromosomes are aligned during CSR. Because the Mut S homolog 4 (Msh4) and Msh5 bind to Holliday junctions and are required for homologous recombination during meiosis in germ cells, we hypothesized these proteins might be involved in trans-chromosomal CSR (trans-CSR). Indeed, Msh4-Msh5 has recently been suggested to have a role in CSR. However, we find a large variety of alternative splice variants of Msh5 mRNA in splenic B cells rather than the full-length form found in testis. Most of these mRNAs are unlikely to be stable, suggesting that Msh5 might not be functional. Furthermore, we find that msh5 nullizygous B cells undergo CSR normally, have unaltered levels of trans-CSR, normal levels of DNA breaks in the Smu region, and normal S-S junctions. We also show that the S-S junctions from cis- and trans-CSR events have similar lengths of junctional microhomology, suggesting trans-CSR occurs by nonhomologous end joining as does intrachromosome (cis)-CSR. From these data, we conclude that Msh5 does not participate in CSR. |
