Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways

Frasca, Daniela; Diaz, Alain; Romero, Maria; Blomberg, Bonnie B.

doi:10.1016/j.exger.2016.12.001

Cited by 160Telomeres, Telomerase, and SenescenceT-cell and B-cell ImmunologyGenetics, Aging, and Longevity in Model Organisms

Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways

Frasca, Daniela, Diaz, Alain, Romero, Maria, Blomberg, Bonnie B.·2017·Experimental Gerontology

DOI 10.1016/j.exger.2016.12.001

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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 have diminished potential to undergo somatic hypermutation.
“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]
Diminished somatic hypermutation in aged B cells could prevent the elderly from generating robust neutralizing antibody titers for clearance and immunity against reinfection.
“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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B CELL SENESCENCE IMPAIRS THE INFLUENZA VACCINE RESPONSE
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Molecular Mechanisms of Compromised B-Cell Functions During Immunosenescence.
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Authors: Frasca, D., Diaz, A., Romero, M., & Blomberg, B. B.
Affiliations: University of Miami (US)
Corresponding author: Frasca, Daniela
ORCID: Frasca, Daniela
Romero, Maria
Blomberg, Bonnie B.
Venue: Experimental Gerontology
Publisher: Elsevier BV
Published: 2017-01
Volume: 87
Issue: Pt A
Pages: 113-120
ISSN: 0531-5565 (ISSN-L)
DOI: 10.1016/j.exger.2016.12.001
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 · 2016: 1
FWCI: 8.59
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Gerontology (publishedVersion)
PubMed (publishedVersion)
Funders: NIH (R01 AG032576, R21 AI096446, R21 AG042826, R56 AG032576)
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: 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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Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways

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