NDLI: Impact of Age on Hypermutation of Immunoglobulin Variable Genes in Humans

Content Provider	Springer Nature Link
Author	Rosner, Karli Winter, David B. Kasmer, Cynthia Skovgaard, Gunhild Lange Tarone, Robert E. Bohr, Vilhelm A. Gearhart, Patricia J.
Copyright Year	2001
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 impaired mismatch repair, was then measured, and there was a strong correlation between the frequency of tandem mutations and microsatellite alterations. The data suggest that individuals vary in their mismatch repair capacity, which can affect the mutational spectra in their antibodies.
Starting Page	102
Ending Page	115
Page Count	14
File Format	PDF
ISSN	02719142
Journal	Journal of Clinical Immunology
Volume Number	21
Issue Number	2
e-ISSN	15732592
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2001-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Immunology Medical Microbiology Internal Medicine Infectious Diseases
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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