Reassessment of the role of Mut S homolog 5 in Ig class switch recombination shows lack of involvement in cis- and trans-switching

Jeroen E.J. Guikema, Carol E. Schrader, Niek G.J. Leus, Anna Ucher, Erin K. Linehan, Uwe Werling, Winfried Edelmann, Janet Stavnezer

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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, ∼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 Sμ 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.

Original languageEnglish (US)
Pages (from-to)8450-8459
Number of pages10
JournalJournal of Immunology
Volume181
Issue number12
DOIs
StatePublished - Dec 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Reassessment of the role of Mut S homolog 5 in Ig class switch recombination shows lack of involvement in cis- and trans-switching'. Together they form a unique fingerprint.

  • Cite this

    Guikema, J. E. J., Schrader, C. E., Leus, N. G. J., Ucher, A., Linehan, E. K., Werling, U., Edelmann, W., & Stavnezer, J. (2008). Reassessment of the role of Mut S homolog 5 in Ig class switch recombination shows lack of involvement in cis- and trans-switching. Journal of Immunology, 181(12), 8450-8459. https://doi.org/10.4049/jimmunol.181.12.8450