Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Feb;8(1):18-25.
doi: 10.1111/j.1474-9726.2008.00443.x. Epub 2008 Nov 5.

B-cell diversity decreases in old age and is correlated with poor health status

Kate L Gibson  1 , Yu-Chang Wu, Yvonne Barnett, Orla Duggan, Robert Vaughan, Elli Kondeatis, Bengt-Olof Nilsson, Anders Wikby, David Kipling, Deborah K Dunn-Walters
Affiliations

B-cell diversity decreases in old age and is correlated with poor health status

Kate L Gibson et al. Aging Cell. 2009 Feb.

Abstract

Older people suffer from a decline in immune system, which affects their ability to respond to infections and to raise efficient responses to vaccines. Effective and specific antibodies in responses from older individuals are decreased in favour of non-specific antibody production. We investigated the B-cell repertoire in DNA samples from peripheral blood of individuals aged 86-94 years, and a control group aged 19-54 years, using spectratype analysis of the IGHV complementarity determining region (CDR)3. We found that a proportion of older individuals had a dramatic collapse in their B-cell repertoire diversity. Sequencing of polymerase chain reaction products from a selection of samples indicated that this loss of diversity was characterized by clonal expansions of B cells in vivo. Statistical analysis of the spectratypes enabled objective comparisons and showed that loss of diversity correlated very strongly with the general health status of the individuals; a distorted spectratype can be used to predict frailty. Correlations with survival and vitamin B12 status were also seen. We conclude that B-cell diversity can decrease dramatically with age and may have important implications for the immune health of older people. B-cell immune frailty is also a marker of general frailty.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Generation of B-cell spectratypes from peripheral blood mononuclear cells. (a) Seminested PCR is performed over the CDR3 region (IGHV-IGHD-IGHJ joining region of the immunoglobulin heavy chain gene), the positions of the primers are indicated by the black bars. The 3′ nested primer is labelled with 6-Fam. The PCR products are electrophoresed on an ABI377 slab gel sequencing system to generate spectratypes (b). The heights of the individual peaks were determined and used to generate graphs where each fragment size is represented as a percentage of the whole (c). The blue dotted line overlaid on the plots represents the median distribution of the young control data set (aged 19–55 years).
Fig. 2
Fig. 2
Age effects on B-cell spectratypes. The line plots for B-cell spectratypes from peripheral blood mononuclear cells of 24 young (a, aged 19–55 years) and 32 old (b, aged 86–94 years) donors are overlaid to show the increased deviation from a normal distribution in some old samples. The dotted line overlaid on the plots represents the median distribution of the young control data set (aged 19–55 years). The SD values for each sample individually are shown, plotted against the donor's age (c).
Fig. 3
Fig. 3
Clonal expansions of B cells in samples with distorted spectratypes, but not in samples with normal spectratypes. The CDR3 regions, covering the IGHV-IGHD-IGHJ joining regions of the immunoglobulin heavy chain gene, were cloned and sequenced from six samples. Sequences highlighted in red are examples of clonal expansions, with the same sequences found in different cloning reactions, or with evidence of intraclonal heterogeneity such as is created by somatic hypermutation during affinity maturation. The spectratype for each sample is shown next to the sequence grouping. Samples A and B are donors aged 95 and 86, respectively, and who have normally-distributed spectratypes. Samples C, D, E and F were aged 90, 86, 86 and 95 years, respectively, and all had distorted spectratypes.
Fig. 4
Fig. 4
Visualization of the relationship between health status and spectratype SD. The SD of each spectratype was calculated as the measure of its distortion and then plotted vs. mean fragment length for ease of visualization (a). Each point is labelled according to the previously determined (Wikby et al., 2002) health data for the donors. vh, very healthy; h, healthy; f, frail. The majority of individuals that are ‘h’ or ‘vh’ have spectratype SDs that are close to mean SD value determined for the younger control group. In contrast, those samples with unusually low or high SDs are entirely those people classified as frail. This observation was independent of the age of the donor (b).
Fig. 5
Fig. 5
Correlations with health and survival. The ΔSD value for each sample was determined as being the difference between the sample value and the mean control value. Donors had previously been classified as frail (f), healthy (h) or very healthy (vh) (Wikby et al., 2002). The difference between the healthy/very healthy and the frail was significant (p = 0.00006 by MWU), as was the difference between people who survived longer than 4 years and those that passed away within 3 years (b, p = 0.035 by MWU). We also found a significant difference in ΔSD between patients with and without vitamin B12 deficiency (c, p = 0.026 by MWU).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Andrès E, Affenberger S, Zimmer J, Vinzio S, Grosu D, Pistol G, Maloisel F, Weitten T, Kaltenbach G, Blicklé JF. Current hematological findings in cobalamin deficiency. Clin. Lab. Haematol. 2006;28:50–56. A study of 201 consecutive patients with documented cobalamin deficiency. - PubMed
    1. Aydar Y, Balogh P, Tew JG, Szakal AK. Follicular dendritic cells in aging, a ‘bottle-neck’ in the humoral immune response. Ageing Res. Rev. 2004;3:15–29. - PubMed
    1. Banerjee M, Sanderson JD, Spencer J, Dunn-Walters DK. Immunohistochemical analysis of ageing human B and T cell populations reveals an age-related decline of CD8 T cells in spleen but not gut-associated lymphoid tissue (GALT) Mech. Ageing Dev. 2000;115:85–99. - PubMed
    1. Banerjee M, Mehr R, Belelovsky A, Spencer J, Dunn-Walters DK. Age- and tissue-specific differences in human germinal center B cell selection revealed by analysis of IgVH gene hypermutation and lineage trees. Eur. J. Immunol. 2002;32:1947–1957. - PubMed
    1. Brochet X, Lefranc MP, Giudicelli V. IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 2008;36:W503–W508. - PMC - PubMed

Publication types

MeSH terms

Substances

  NODES
twitter 2