AUTHOR=Díez Paula , Pérez-Andrés Martín , Bøgsted Martin , Azkargorta Mikel , García-Valiente Rodrigo , Dégano Rosa M. , Blanco Elena , Mateos-Gomez Sheila , Bárcena Paloma , Santa Cruz Santiago , Góngora Rafael , Elortza Félix , Landeira-Viñuela Alicia , Juanes-Velasco Pablo , Segura Victor , Manzano-Román Raúl , Almeida Julia , Dybkaer Karen , Orfao Alberto , Fuentes Manuel TITLE=Dynamic Intracellular Metabolic Cell Signaling Profiles During Ag-Dependent B-Cell Differentiation JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.637832 DOI=10.3389/fimmu.2021.637832 ISSN=1664-3224 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.