Frontiers in Immunology (Mar 2021)

Dynamic Intracellular Metabolic Cell Signaling Profiles During Ag-Dependent B-Cell Differentiation

  • Paula Díez,
  • Paula Díez,
  • Martín Pérez-Andrés,
  • Martin Bøgsted,
  • Mikel Azkargorta,
  • Rodrigo García-Valiente,
  • Rosa M. Dégano,
  • Elena Blanco,
  • Sheila Mateos-Gomez,
  • Paloma Bárcena,
  • Santiago Santa Cruz,
  • Rafael Góngora,
  • Félix Elortza,
  • Alicia Landeira-Viñuela,
  • Pablo Juanes-Velasco,
  • Victor Segura,
  • Raúl Manzano-Román,
  • Julia Almeida,
  • Karen Dybkaer,
  • Alberto Orfao,
  • Manuel Fuentes,
  • Manuel Fuentes

DOI
https://doi.org/10.3389/fimmu.2021.637832
Journal volume & issue
Vol. 12

Abstract

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Human B-cell differentiation has been extensively investigated on genomic and transcriptomic grounds; however, no studies have accomplished so far detailed analysis of antigen-dependent maturation-associated human B-cell populations from a proteomic perspective. Here, we investigate for the first time the quantitative proteomic profiles of B-cells undergoing antigen-dependent maturation using a label-free LC-MS/MS approach applied on 5 purified B-cell subpopulations (naive, centroblasts, centrocytes, memory and plasma B-cells) from human tonsils (data are available via ProteomeXchange with identifier PXD006191). Our results revealed that the actual differences among these B-cell subpopulations are a combination of expression of a few maturation stage-specific proteins within each B-cell subset and maturation-associated changes in relative protein expression levels, which are related with metabolic regulation. The considerable overlap of the proteome of the 5 studied B-cell subsets strengthens the key role of the regulation of the stoichiometry of molecules associated with metabolic regulation and programming, among other signaling cascades (such as antigen recognition and presentation and cell survival) crucial for the transition between each B-cell maturation stage.

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