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, increased apoptosis and compromised function were observed in highly proliferative tissues including skin, hematopoietic and reproductive systems.
“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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- 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
- Health Sciences › Medicine › Physiology › 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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