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- W2059494328 abstract "To determine the impact of somatic hypermutation and selective influences on the VH gene repertoire in SLE, the mutational frequency and pattern of mutations in nonproductively and productively rearranged VH genes obtained from genomic DNA of individual CD 19+ B cells were analyzed in a patient with SLE.The mutational frequencies of nonproductive (6.54×10−2) as well as of productive (4.38×10−2) VH rearrangements were significantly higher in the SLE patient than in normal controls (3.8×10−2 p<0.001 and 3.3×10−2; p<0.001, respectively). Analysis of nonproductive rearrangements documented only minor abnormalities of the targeting of the mutator in the SLE patient. The majority of “mutational hot spots”, although different than in normals, appeared in the CDRs and an increased frequency of mutations in RGYW/WRCY sequences was observed. Moreover, no biases in base pair changes were found in the nonproductive repertoire.In contrast, there was a selection against A and T mutations and towards G mutations within the productive repertoire. Importantly, there were no significant differences in the R/S ratios of mutations within the FRs between the nonproductive and productive repertoire consistent with abnormalities in elimination of B cells expressing VH genes with these mutations. The result of this abnormality was a significantly higher R/S ratio of the VHgenes in the productive repertoire of the SLE patient compared to normals (p<0.05).These data indicate that the mutational machinery was markedly enhanced in this SLE patient but exhibited nearly normal targeting, whereas selective influences were abnormal. These findings suggest that both enhanced mutational activity and disturbances in selection may have played a role in the emergence of autoreactivity in this SLE patient" @default.
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- W2059494328 date "2001-01-01" @default.
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- W2059494328 title "Enhanced Mutational Activity and Disturbed Selection of Mutations in V<sub>H</sub>Gene Rearrangements in a Patient with Systemic Lupus Erythematosus" @default.
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- W2059494328 doi "https://doi.org/10.3109/08916930108994110" @default.
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