Mismatch Repair Deficiency Interferes with the Accumulation of Mutations in Chronically Stimulated B Cells and Not with the Hypermutation Process

Primary responses to the hapten phenyloxazolone and chronic responses to environmental antigens occuring in Peyer’s patches were analyzed in two different mismatch repair–deficient backgrounds. Paradoxically, whereas primary responses were found normal in MSH2- and only slightly diminished in PMS2-d...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1998-07, Vol.9 (1), p.127-134
Main Authors: Frey, Stéphane, Bertocci, Barbara, Delbos, Frédéric, Quint, Laurent, Weill, Jean-Claude, Reynaud, Claude-Agnès
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases
Animals
B-Lymphocytes
Base Sequence
Cell Line
DNA Repair
DNA Repair Enzymes
DNA-Binding Proteins
Genes, Immunoglobulin
Germinal Center
Haptens - administration & dosage
Mice
Mice, Knockout
Microsatellite Repeats
Mismatch Repair Endonuclease PMS2
Molecular Sequence Data
Mutation
MutS Homolog 2 Protein
Oxazolone - administration & dosage
Oxazolone - analogs & derivatives
Peyer's Patches
Proteins - genetics
Proteins - physiology
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
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Summary:Primary responses to the hapten phenyloxazolone and chronic responses to environmental antigens occuring in Peyer’s patches were analyzed in two different mismatch repair–deficient backgrounds. Paradoxically, whereas primary responses were found normal in MSH2- and only slightly diminished in PMS2-deficient mice, mutations in Peyer’s patch B cells from both k.o. animals were reduced three times, the subset of Peyer’s patch B cells with highly mutated sequences being specifically missing in the mismatch repair–deficient context. Strikingly, germinal center B cells from Peyer’s patches of k.o. animals showed microsatellite instability at an unprecedented level. We thus propose that the amount of DNA damages generated prevents these cells from recycling in germinal centers and that mismatch repair deficiency is only the indirect cause of the lower mutation incidence observed.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80594-4