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

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

Research output: Contribution to journalArticle

38 Scopus citations

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 (p16INK4). 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.

Original languageEnglish (US)
Pages (from-to)113-120
Number of pages8
JournalExperimental Gerontology
Volume87
DOIs
StatePublished - Jan 1 2017

Keywords

  • Aging
  • B cells
  • Inflammation
  • SASP
  • Vaccine responses

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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