tetano
Editor, Senior Moderator
Exp Gerontol. 2016 Dec 6;87(Pt A):113-120. doi: 10.1016/j.exger.2016.12.001. [Epub ahead of print]
[h=1]Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways.[/h] Frasca D[SUP]1[/SUP], Diaz A[SUP]2[/SUP], Romero M[SUP]2[/SUP], Blomberg BB[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 [na?ve, 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[SUP]INK4[/SUP]). 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.
Copyright ? 2016 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Aging; B cells; Inflammation; SASP; Vaccine responses
PMID: 27931848 DOI: 10.1016/j.exger.2016.12.001
[PubMed - as supplied by publisher]
[h=1]Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways.[/h] Frasca D[SUP]1[/SUP], Diaz A[SUP]2[/SUP], Romero M[SUP]2[/SUP], Blomberg BB[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 [na?ve, 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[SUP]INK4[/SUP]). 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.
Copyright ? 2016 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Aging; B cells; Inflammation; SASP; Vaccine responses
PMID: 27931848 DOI: 10.1016/j.exger.2016.12.001
[PubMed - as supplied by publisher]