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Impaired germinal center reaction in mice with short telomeres
Open accessAbstract
Reduction of germinal center reactivity is a landmark of immunosenescence and contributes to immunological dysfunction in the elderly. Germinal centers (GC) are characterized by extensive clonal expansion and selection of B lymphocytes to generate the pool of memory B cells. Telomere maintenance by telomerase has been proposed to allow the extensive proliferation undergone by B lymphocytes in the GC during the immune response. We show here that late generation mTR(-/-) mice, which lack the mouse telomerase RNA (mTR) and have short telomeres, present a dramatic reduction in GC number following antigen immunization. Upon immunization with an antigen, wild-type splenocyte telomeres are elongated and this is accompanied by a high expression of the telomerase catalytic subunit in the spleen GC. In contrast, telomerase-deficient mTR(-/-) splenocytes show telomere shortening after immunization, presumably due to cell proliferation in the absence of telomerase. All together, these results demonstrate the importance of telomere maintenance for antibody-mediated immune responses and support the notion that telomere elongation detected in wild-type spleens following immunization is mediated by telomerase.
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“By the sixth generation (G6), increased apoptosis and compromised function were observed in highly proliferative tissues including skin, hematopoietic and reproductive systems31, 42-44.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [43]
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Metadata
- Authors
- Herrera, E., Martínez‐A, C., & Blasco, M. A.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Blasco, María A.
- Venue
- The EMBO Journal
- Published
- 2000-02-01
- Volume
- 19
- Issue
- 3
- Pages
- 472-481
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC305584
- OpenAlex
- W1995491393
- Cited by
- 144
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 2 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 3
- FWCI
- 11.82
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- germinal center, telomere shortening, telomerase, immunosenescence, B cell proliferation, antibody-mediated immune response, memory B cells, telomere maintenance
- MeSH terms
- Animals, B-Lymphocytes, Cell Cycle, Chromosomes, Flow Cytometry, Histocytochemistry, Immunization, Lipopolysaccharides, Mitogens, Spleen, Telomere, Apoptosis, In Situ Hybridization, Fluorescence, Mice, Knockout, Germinal Center, Telomerase, Mice
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