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

Front Immunol. 2021 Mar 30:12:637832. doi: 10.3389/fimmu.2021.637832. eCollection 2021.

Abstract

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.

Keywords: B-cell differentiation; centroblast; centrocyte; memory B cell; naive B cell; quantitative proteomics; transcriptomics integration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens / immunology*
  • B-Lymphocyte Subsets / cytology*
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Humans
  • Lymphocyte Activation / immunology
  • Male
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • Proteome / genetics
  • Signal Transduction / immunology*
  • Transcriptome / genetics
  • Young Adult

Substances

  • Antigens
  • Proteome