TY - JOUR
T1 - Age-related accumulation of Ig VH gene somatic mutations in peripheral B cells from aged humans
AU - Chong, Y.
AU - Ikematsu, Hideyuki
AU - Yamaji, K.
AU - Nishimura, M.
AU - Kashiwagi, S.
AU - Hayashi, J.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - 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 μ and 164 γ transcripts with VH5 family genes, were analysed for somatic hypermutation and VHDJH recombinational features. Unmutated and mutated μ 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 μ transcripts were 39% and 42%, respectively. D and JH 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. γtranscripts, 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 VHDJH recombinational diversity was preserved, but that the accumulation of somatic mutations in the IgG VH 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.
AB - 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 μ and 164 γ transcripts with VH5 family genes, were analysed for somatic hypermutation and VHDJH recombinational features. Unmutated and mutated μ 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 μ transcripts were 39% and 42%, respectively. D and JH 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. γtranscripts, 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 VHDJH recombinational diversity was preserved, but that the accumulation of somatic mutations in the IgG VH 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.
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U2 - 10.1046/j.1365-2249.2003.02185.x
DO - 10.1046/j.1365-2249.2003.02185.x
M3 - Article
C2 - 12823279
AN - SCOPUS:0038047062
SN - 0009-9104
VL - 133
SP - 59
EP - 66
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 1
ER -