Age-related impaired affinity maturation and differential D-JH gene usage in human VH6-expressing B lymphocytes from healthy individuals.
To elucidate the basic molecular events underlying humoral immunity during ontogeny and senescence, we analyzed a panel of 179 polymerase chain reaction-derived VH6-D-JH rearrangements from cord blood, peripheral blood, and spleen. Nucleotide sequence analysis of the CDR3 region shows that there is a difference in D and JH gene usage in functional rearrangements between lymphocytes from peripheral blood and spleen. Analysis of the VH6 gene shows that the mutational frequencies rise from 0.81% in cord blood to 1.96% in peripheral blood lymphocytes derived from young adults, and decrease to 0.80% in samples from individuals older than 50 years. The number of rearrangements carrying mutations follows a similar pattern: 22% in cord blood, 73% in the age group 20-49 years, and 57% in the age group over 50 years. The mutational frequencies among the mutated genes are, however, similar for cord blood and young adults, 2.76% and 2.51%, respectively, and 1.3% in older adults. These data show an age-related impaired affinity maturation which might relate to the decrease in immunological responsiveness among the elderly.
van Dijk-Härd
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Division for Clinical Immunology, Karolinska Institute, Huddinge Hospital, Sweden.
Söderström
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Feld
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Holmberg
D
D
Lundkvist
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D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D000915:Antibody Affinity / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000502:physiology*; D005803:Genes, Immunoglobulin; D014644:Genetic Variation / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008875:Middle Aged; D009928:Organ Specificity / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region