Age-Associated Changes in Antibody-Forming Cells (B Cells)

Schulze, Dan H.; Goidl, Edmond A.

doi:10.3181/00379727-196-43186

Cited by 9 publications

(3 citation statements)

References 30 publications

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“…An age‐associated decrease in the average affinity of antibody responses has been known for many years 18 . However, the underlying molecular cause(s) of these changes remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Alterations in CDR3 diversity with ageing could be involved in the age‐associated decrease in the affinity of antibody responses known for many years 18 . 27 As regards CDR3 diversity, aged mice show no significant changes in nucleotide addition or deletion at VH–D–JH junctions; however, a marked shift in D‐segment family utilization between aged and young mice has been found 28 .…”

Section: Discussionmentioning

confidence: 99%

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Age‐related alterations of somatic hypermutation and CDR3 lengths in human Vκ4‐expressing B lymphocytes

Troutaud

Drouet²,

Decourt³

et al. 1999

Immunology

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SUMMARYThe lower avidity and/or affinity of antibodies generated by an aged immune system could be attributed to two major changes in the antibody repertoire: a shift in germline gene usage and a decrease in the rate of immunoglobulin hypermutation. In an attempt to identify the mechanisms involved in the observed humoral immune deficiency in the elderly, we studied whether differences in the somatic diversity of a particular Vk region occurred with ageing. By using the polymerase chain reaction and sequencing, we analysed and compared Vk4-Jk rearrangements isolated from young (mean age 21 years) and aged (mean age 83 years) healthy adults. Mutations in the Vk4 gene compared with the germline sequence were determined as well as the length and structure of the CDR3 sequence. We analysed in detail various mechanisms contributing to CDR3 and Vk variability in rearrangements involving the Vk4 gene. Our data revealed that, despite strong individual variations, significantly lower levels of somatic mutation were found in the aged group, both for complementarity-determining regions (CDRs) and framework regions (FRs) encoding Vk4 sequences. This decrease mostly affected mutations responsible for replacements and thus resulted in a lowered somatic diversification of the encoded Vk4 proteins in aged individuals. Moreover, comparison of the CDR3 regions of the Vk4-Ck cDNA revealed changes in lightchain junctional diversity that correlated with age. Altogether these data suggest an impaired light-chain somatic diversity in connection with human senescence.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Age‐related alterations of somatic hypermutation and CDR3 lengths in human Vκ4‐expressing B lymphocytes

Troutaud

Drouet²,

Decourt³

et al. 1999

Immunology

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“…Impaired humoral immunity in the elderly is mainly caused by dysfunction of T cells that regulate B-cell activation and differentiation (79,81,83). Production and affinity maturation of antibody in response to antigen decline in the elderly (83,87,88). Changes in function of antigen-presenting cells such as macrophages and dendric cells are controversial (89)(90)(91).…”

Section: Infectionsmentioning

confidence: 99%

Cancer Chemotherapy in the Elderly

Sekine

Fukuda

Kunitoh

et al. 1998

Japanese Journal of Clinical Oncology

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As the geriatric population is growing, it is increasingly important to be familiar with chemotherapy for the elderly. Age-related changes in pharmacokinetics are documented for doxorubicin, etoposide, ifosfamide, daunorubicin, mitomycin, cisplatin and methotrexate. The hematological toxicity of most standard-dose chemotherapy is not affected by age in patients with normal organic functions and good performance status, although increased toxicity with aging is suggested in the use of actinomycin-D, etoposide, vinblastin, methotrexate, methyl-CCNU, doxorubicin and mitomycin, and in dose-intensive chemotherapy. Among non-hematological toxicities, only doxorubicin-induced cardiomyopathy and bleomycin-induced pulmonary toxicity are demonstrated to be accelerated in the elderly. There is no evidence that advanced age decreases the efficacy of chemotherapy for tumors, except for Hodgkin's disease and acute leukemia. These results suggest that advanced chronological age alone is not always associated with severe toxicity and poor prognosis, and that many elderly patients with cancer will benefit from chemotherapy. To answer questions regarding the optimal chemotherapy regimen, dose and intensity in this population, the influence of age should be analyzed in a multivariate approach in future studies.

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