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Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways
Abstract
The percentage of late/exhausted memory (LM) B cells increases with age and we show here that this is associated with a lower influenza vaccine response. To identify novel contributors to the phenotypic and functional changes observed in aged B cells, we sorted the major peripheral B cell subsets [naïve, IgM memory, switched memory (swIg) and late/exhausted memory (LM)] and determined their percentages in the peripheral blood as well as their level of immune activation by measuring basal levels of expression of multiple senescence-associated secretory phenotype (SASP) markers, such as pro-inflammatory cytokines (TNF-α/IL-6/IL-8), inflammatory micro-RNAs (miRs, miR-155/16/93), cell cycle regulators (p16 INK4). We found that only memory B cells express SASP markers, and especially the LM B cell subset, which is also showing spontaneous activation of AMP-activated protein kinase (AMPK), the energy sensing enzyme which is ubiquitously expressed in mammalian cells. LM B cells, but not IgM memory B cells, activate a p38MAPK signaling pathway, downstream of AMPK, leading to the expression of SASP mediators, while class switch recombination is downregulated. These data show that some B cell subsets are more inflammatory than others, that they are pre-activated and that this signaling through metabolic pathways is associated with a senescence phenotype, demonstrating for the first time in human B lymphocytes the link between aging, cellular senescence, SASP and metabolism.
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“The quality of the humoral immune response declines with age, as aged B cells display a diminished potential to undergo somatic hypermutation154, which could prevent the aged from generating robust neutralizing antibody titers to aid the clearance of natural infection and generate effective immunity against re-infections.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [154]
In the citing paper
“The quality of the humoral immune response declines with age, as aged B cells display a diminished potential to undergo somatic hypermutation154, which could prevent the aged from generating robust neutralizing antibody titers to aid the clearance of natural infection and generate effective immunity against re-infections.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [154]
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Metadata
- Authors
- Frasca, D., Diaz, A., Romero, M., & Blomberg, B. B.
- Affiliations
- University of Miami (US)
- Corresponding author
- Frasca, Daniela
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 87
- Issue
- Pt A
- Pages
- 113-120
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2559849490
- Cited by
- 160
- References
- 57
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 21 · 2023: 14 · 2022: 21 · 2021: 30 · 2020: 15 · 2019: 13 · 2018: 8 · 2017: 10
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (R01 AG032576, R21 AI096446, R21 AG042826, R56 AG032576)
- 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
- senescence-associated secretory phenotype, cellular senescence, B cell aging, influenza vaccine response, AMPK, p38 MAPK signaling, metabolic signaling, class switch recombination, p16INK4, inflammatory cytokines, human B lymphocytes
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Cell Line, Female, Hemagglutination Inhibition Tests, Humans, Male, Middle Aged, Biomarkers, B-Lymphocyte Subsets, Cytokines, Cellular Senescence, MAP Kinase Signaling System, MicroRNAs, Metabolic Networks and Pathways, AMP-Activated Protein Kinases
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