Role for mismatch repair proteins Msh2, Mlh1, and Pms2 in immunoglobulin class switching shown by sequence analysis of recombination junctions
UMass Chan AffiliationsDepartment of Molecular Genetics and Microbiology
Document TypeJournal Article
*Base Pair Mismatch
*DNA Repair Enzymes
*Immunoglobulin Class Switching
Mice, Inbred C57BL
Molecular Sequence Data
MutS Homolog 2 Protein
Sequence Homology, Nucleic Acid
splenic B cells
antibody heavy chain isotypes
Medicine and Health Sciences
MetadataShow full item record
AbstractB cells from mice deficient in mismatch repair (MMR) proteins show decreased ability to undergo class switch recombination in vitro and in vivo. The deficit is not accompanied by any reduction in cell viability or alterations in the cell cycle in B cells cultured in vitro. To assess the role of MMR in switching we examined the nucleotide sequences of Smicro-Sgamma3 recombination junctions in splenic B cells induced in culture to switch to IgG3. The data demonstrate clear differences in the sequences of switch junctions in wild-type B cells in comparison with Msh2-, Mlh1-, and Pms2-deficient B cells. Sequences of switch junctions from Msh2-deficient cells showed decreased lengths of microhomology between Smicro and Sgamma3 relative to junctions from wild-type cells and an increase in insertions, i.e., nucleotides which do not appear to be derived from either the Smicro or Sgamma3 parental sequence. By contrast, 23% of junctions from Mlh1- and Pms2-deficient cells occurred at unusually long stretches of microhomology. The data indicate that MMR proteins are directly involved in class switching and that the role of Msh2 differs from that of Mlh1 and Pms2.
J Exp Med. 2002 Feb 4;195(3):367-73.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/50659
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