High TNF-α levels in resting B cells negatively correlate with their response

Daniela Frasca, Alain Diaz, Maria Romero, Ana Marie Landin, Bonnie B. Blomberg

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Aging significantly decreases the influenza vaccine-specific response as we and others have previously shown. Based on our previous data in aged mice, we hypothesize that the inflammatory status of the individual and of B cells themselves would impact B cell function. We here show that the ability to generate a vaccine-specific antibody response is negatively correlated with levels of serum TNF-α. Moreover, human unstimulated B cells from elderly make higher levels of TNF-α than those from young individuals, and these positively correlate with serum TNF-α levels. These all negatively correlate with B cell function, measured by activation-induced cytidine deaminase, the enzyme of class switch recombination and somatic hypermutation. Only memory B cells (either IgM or switched), but not naïve B cells, make appreciable levels of TNF-α and more in elderly as compared to young individuals. Finally, an anti-TNF-α antibody can increase the response in cultured B cells from the elderly, suggesting that TNF-α secreted by memory B cells affects IgM memory B cells and naïve B cells in an autocrine and/or paracrine manner. Our results show an additional mechanism for reduced B cell function in the elderly and propose B cell-derived TNF-α as another predictive biomarker of in vivo and in vitro B cell responses.

Original languageEnglish (US)
Pages (from-to)116-122
Number of pages7
JournalExperimental Gerontology
Volume54
DOIs
StatePublished - Jun 2014

Keywords

  • Aging
  • B cells
  • Inflammation
  • Vaccine responses

ASJC Scopus subject areas

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

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