Age-related accumulation of Ig VH gene somatic mutations in peripheral B cells from aged humans

To investigate age-related alterations in human humoral immunity, we analysed Ig heavy chain variable region genes expressed by peripheral B cells from young and aged individuals. Three hundred and twenty-seven cDNA sequences, 163 mu and 164 gamma transcripts with V-H 5 family genes, were analysed for somatic hypermutation and V-H DJ(H) recombinational features. Unmutated and mutated mu transcripts were interpreted as being from naive and memory IgM B cells, respectively. In young and aged individuals, the percentages of naive IgM among total mu transcripts were 39% and 42%, respectively. D and J(H) segment usage in naive IgM from aged individuals was similar to that from young individuals. The mutational frequencies of memory IgM were similar in young and aged individuals. gamma transcripts, which are regarded as being from memory IgG B cells, showed a significantly higher mutational frequency (7.6%) in aged than in young individuals (5.8%) (P < 0.01). These findings suggest that V-H DJ(H) recombinational diversity was preserved, but that the accumulation of somatic mutations in the IgG V-H region was increased in aged humans. The accumulation of somatic mutations in IgG B cells during ageing may imply that an age-related alteration exists in the selection and/or maintenance of peripheral memory B cells.