Stable telomere length and telomerase expression from naı̈ve to memory B-lymphocyte differentiation

Son, Ni Huiping; Joyce, Bradley R.; Hieatt, Arron; Chrest, Francis J.; Yanovski, Jack A.; Weng, Nan‐ping

doi:10.1016/s0047-6374(03)00018-6

Cited by 39 publications

(32 citation statements)

References 19 publications

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“…Furthermore, it is also known that telomerase is constitutively expressed in germ-line cells [54,57,58] and is absent or low expressed in adult differentiated cells. It is believed that the up-regulation of telomerase might play a role in maintaining lymphocyte replicative potential and function [59]. For this reason, we examined the relative telomerase activity (RTA) after stimulation with CpG/␣-IgG/CD40 in DN B lymphocytes from young and elderly subjects.…”

Section: Discussionmentioning

confidence: 99%

Double negative (CD19+IgG+IgD−CD27−) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer's disease patients

et al. 2014

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a b s t r a c tImmunosenescence is characterized by the impairment of humoral immunity with changes in the memory/naive B cell compartment. In particular we have previously reported the percentage increase of a Memory IgD − CD27 − (Double Negative, DN) B cell population in aged people. In this study, we have further characterized DN B cells with the aim to better understand their contribution to immunosenescence. As DN B cells show a poor ability to proliferate in vitro, we have evaluated the expression of the inhibitory receptors CD307d and CD22 on these cells from young and old individuals. In addition we have evaluated the ability to activate DN B cells by the simultaneous use of innate (CpG) and adaptive (␣-Ig/CD40) ligands. Our data demonstrate that the refractoriness to proliferate of DN B cells does not depend on the expression of inhibitory receptors, but it is due to the kind of stimulation. Indeed, when DN B cells are stimulated engaging both BCR and TLR9, they become able to proliferate and reactivate the telomerase enzyme. In the present study, we have also compared the telomerase activity in a group of people genetically advantaged for longevity as centenarian offspring (CO) and in a group of moderate-severe Alzheimer's disease (AD) patients, who represent a model of unsuccessful aging. Our study suggests that telomerase reactivation of DN B cells, as well as their number and ability in activating, depend essentially by the biological age of the subjects studied, so the evaluation of DN B cells might allow to gain insight to healthy and unsuccessful aging.

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Section: Discussionmentioning

confidence: 99%

Double negative (CD19+IgG+IgD−CD27−) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer's disease patients

et al. 2014

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“…Additionally, there is no difference in TL between naïve and memory B cell populations, and the naïve-to-memory B-cell transition is not associated with telomere loss [102] . This may be due to the unique microenvironment of the germinal center where naïve B-cell differentiation takes place [103] .…”

Section: Proliferation-induced Telomere Loss In Lymphocytesmentioning

confidence: 90%

Telomeres and Immunological Diseases of Aging

et al. 2009

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A defining feature of the eukaryotic genome is the presence of linear chromosomes. This arrangement, however, poses several challenges with regard to chromosomal replication and maintenance. To prevent the loss of coding sequences and to suppress gross chromosomal rearrangements, linear chromosomes are capped by repetitive nucleoprotein structures, called telomeres. Each cell division results in a progressive shortening of telomeres that, below a certain threshold, promotes genome instability, senescence, and apoptosis. Telomeric erosion, maintenance, and repair take center stage in determining cell fate. Cells of the immune system are under enormous proliferative demand, stressing telomeric intactness. Lymphocytes are capable of upregulating telomerase, an enzyme that can elongate telomeric sequences and, thus, prolong cellular lifespan. Therefore, telomere dynamics are critical in preserving immune function and have become a focus for studies of immunosenescence and autoimmunity. In this review, we describe the role of telomeric nucleoproteins in shaping telomere architecture and in suppressing DNA damage responses. We summarize new insights into the regulation of telomerase activity, hereditary disorders associated with telomere dysfunction, the role of telomere loss in immune aging, and the impact of telomere dysfunction in chronic inflammatory disease.

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“…B lymphocytes show slower telomere loss than T lymphocytes, with no real difference between naïve and memory B cell subsets (351,352,398). Germinal center B cells demonstrate the highest telomerase activity.…”

Section: Telomere Attrition In Immune Senescencementioning

confidence: 98%

Aging and Immune Function: Molecular Mechanisms to Interventions

Ponnappan

2011

Antioxidants & Redox Signaling

290

266

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The immune system of an organism is an essential component of the defense mechanism aimed at combating pathogenic stress. Age-associated immune dysfunction, also dubbed ''immune senescence,'' manifests as increased susceptibility to infections, increased onset and progression of autoimmune diseases, and onset of neoplasia. Over the years, extensive research has generated consensus in terms of the phenotypic and functional defects within the immune system in various organisms, including humans. Indeed, age-associated alterations such as thymic involution, T cell repertoire skewing, decreased ability to activate naïve T cells and to generate robust memory responses, have been shown to have a causative role in immune decline. Further, understanding the molecular mechanisms underlying the generation of proteotoxic stress, DNA damage response, modulation of ubiquitin proteasome pathway, and regulation of transcription factor NFkB activation, in immune decline, have paved the way to delineating signaling pathways that cross-talk and impact immune senescence. Given the role of the immune system in combating infections, its effectiveness with age may well be a marker of health and a predictor of longevity. It is therefore believed that a better understanding of the mechanisms underlying immune senescence will lead to an effective interventional strategy aimed at improving the health span of individuals. Antioxid. Redox Signal. 14, 1551-1585.

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Stable telomere length and telomerase expression from naı̈ve to memory B-lymphocyte differentiation

Cited by 39 publications

References 19 publications

Double negative (CD19+IgG+IgD−CD27−) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer's disease patients

Double negative (CD19+IgG+IgD−CD27−) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer's disease patients

Telomeres and Immunological Diseases of Aging

Aging and Immune Function: Molecular Mechanisms to Interventions

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