PMID: 11332649May 3, 2001Paper

Impact of age on hypermutation of immunoglobulin variable genes in humans

Journal of Clinical Immunology
K RosnerPatricia J Gearhart

Abstract

Chronological aging is associated with an accumulation of DNA mutations that results in cancer formation. The effect of aging on spontaneous mutations in humans is difficult to study because mutations are infrequent in the overall genome and tumors are relatively rare. In contrast, somatic mutations in immunoglobulin variable genes are abundant and can be studied in peripheral blood lymphocytes. To determine if aging alters the frequency and pattern of hypermutation, we sequenced 331 cDNA clones with rearranged V(H)6 genes and compared 452 mutations from young humans to 570 mutations from old humans. There were more mutated clones in the young population compared to the old population. Among the mutated clones, the frequency, location, and types of substitutions were similar between the young and the old groups. However, the ratio of replacement-to-silent mutations was much higher in the complementarity-determining regions of heavy chains from old people, which indicates that their B cells had been selected by antigen. Among individuals, there was variability in the frequency of tandem mutations, which we have observed in mice defective for the PMS2 mismatch repair protein. Microsatellite variability in DNA, which is caused by ...Continue Reading

Citations

Nov 26, 2009·Biogerontology·Alexander AdemokunDeborah Dunn-Walters
Dec 8, 2015·PLoS Biology·Patricia J GearhartLisa M Russell Knode
Jun 26, 2003·Clinical and Experimental Immunology·Y ChongJ Hayashi
Mar 31, 2004·The Journal of Experimental Medicine·Xianmin ZengPatricia J Gearhart
Oct 28, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Takao KoderaConstantin Bona
Apr 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniela FrascaBonnie B Blomberg
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vladimir I MayorovPatricia J Gearhart
Apr 6, 2004·Immunology and Cell Biology·Edward J SteeleRobert V Blanden
Nov 13, 2013·Immunology and Cell Biology·Michelle A Linterman
Dec 9, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ang CuiSteven H Kleinstein
Jun 25, 2015·Microbiology Spectrum·Joyce K HwangLeng-Siew Yeap

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