Abstract
Rearranged immunoglobulin variable genes are extensively mutated after stimulation of B lymphocytes by antigen. Mutations are likely generated by an error-prone DNA polymerase, and the mismatch repair pathway may process the mispairs. To examine the role of the MSH2 mismatch repair protein in hypermutation, Msh2(-/-) mice were immunized with oxazolone, and B cells were analyzed for mutation in their V(κ)Ox1 light chain genes. The frequency of mutation in the repair-deficient mice was similar to that in Msh2(+/+) mice, showing that MSH2-dependent mismatch repair does not cause hypermutation. However, there was a striking bias for mutations to occur at germline G and C nucleotides. The results suggest that the hypermutation pathway frequently mutates G-C pairs, and a MSH2-dependent pathway preferentially corrects mismatches at G and C.
Original language | English (US) |
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Pages (from-to) | 1745-1750 |
Number of pages | 6 |
Journal | Journal of Experimental Medicine |
Volume | 187 |
Issue number | 11 |
DOIs | |
State | Published - Jun 1 1998 |
Externally published | Yes |
Keywords
- Biological sciences
- DNA repair
- Genes, immunoglobulin
- Genetics
- Mutation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology