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- W2108752404 abstract "The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin ( Ig ) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a ‘homeologous’ recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6 −/− and Pms2 −/− DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVλ GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of ‘homeologous’ recombination insensitive to MMR." @default.
- W2108752404 created "2016-06-24" @default.
- W2108752404 creator A5005146671 @default.
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- W2108752404 creator A5088266515 @default.
- W2108752404 date "2013-01-10" @default.
- W2108752404 modified "2023-10-01" @default.
- W2108752404 title "MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils" @default.
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- W2108752404 doi "https://doi.org/10.1093/nar/gks1470" @default.
- W2108752404 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3597665" @default.
- W2108752404 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23314153" @default.
- W2108752404 hasPublicationYear "2013" @default.
- W2108752404 type Work @default.