Metabolomics of B to plasma cell differentiation

Jose Manuel Garcia-Manteiga, Silvia Mari, Markus Godejohann, Manfred Spraul, Claudia Napoli, Simone Cenci, Giovanna Musco, Roberto Sitia

Research output: Contribution to journalArticle

Abstract

When small B lymphocytes bind antigen in the context of suitable signals, a profound geno-proteomic metamorphosis is activated that generates antibody-secreting cells. To study the metabolic changes associated with this differentiation program, we compared the exometabolome of differentiating murine B lymphoma cells and primary B cells by monodimensional proton nuclear magnetic resonance spectroscopy and mass spectrometry coupled to liquid chromatography. Principal component analysis, a multivariate statistical analysis, highlighted metabolic hallmarks of the sequential differentiation phases discriminating between the proliferation and antibody secreting phases and revealing novel metabolic pathways. During proliferation, lactate production increased together with consumption of essential amino acids; massive Ig secretion was paralleled by alanine and glutamate production, glutamine being used as carbon and energy sources. Notably, ethanol and 5′-methylthioadenosine were produced during the last phase of protein secretion and the proliferative burst, respectively. Our metabolomics results are in agreement with previous genoproteomics studies. Thus, metabolic profiling of extracellular medium is a useful tool to characterize the functional state of differentiating B cells and to identify novel underlying metabolic pathways.

Original languageEnglish
Pages (from-to)4165-4176
Number of pages12
JournalJournal of Proteome Research
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 2 2011

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Keywords

  • B lymphocytes
  • immunoglobulin footprinting
  • metabolic profiling
  • metabolomics
  • MS
  • NMR
  • plasma cells
  • protein secretion

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Garcia-Manteiga, J. M., Mari, S., Godejohann, M., Spraul, M., Napoli, C., Cenci, S., Musco, G., & Sitia, R. (2011). Metabolomics of B to plasma cell differentiation. Journal of Proteome Research, 10(9), 4165-4176. https://doi.org/10.1021/pr200328f