title: Proteome profiling suggests a pro-inflammatory role for plasma cells through release of high-mobility group box 1 protein.
abstract: The final step of B-cell maturation is to differentiate into plasma cells, a process that is accompanied by gross changes in subcellular organization to enable antibody secretion. To better understand this critical step in mounting a humoral immune response, we analyzed proteome dynamics during plasma cell differentiation with combined 2-DE/MS. Thirty-two identified protein spots changed in relative abundance when lipopolysaccharide (LPS)-stimulated primary B cells differentiated into antibody-secreting plasma cells. A correlative analysis of protein and transcript abundance suggested that one third of these proteins are post-transcriptionally regulated. Apart from ER-resident chaperones, lipid metabolic enzymes, and translation initiation factors, we identified several proteins that had not been previously studied in plasma cells. Among them is the transiently upregulated proteasome activator (PA) 28γ, a component of the putative nuclear proteasome. Additionally, we discovered that the non-canonical inflammatory cytokine high-mobility group box 1 (HMG1) was released from plasma cells into the extracellular milieu. This suggests a novel role for plasma cells as pro-inflammatory mediators, which has important implications for various autoimmune diseases and chronic inflammation.
authors.affiliation: Division of Molecular Immunology, Department of Internal Medicine, Nikolaus-Fiebiger-Center for Molecular Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Vettermann
authors.forename: Dennis
authors.initials: D
authors.lastname: Castor
authors.forename: Andrea
authors.initials: A
authors.lastname: Mekker
authors.forename: Bertran
authors.initials: B
authors.lastname: Gerrits
authors.forename: Michael
authors.initials: M
authors.lastname: Karas
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D056724:Immunity, Humoral / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020543:Proteome / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D001324:Autoantigens; D039642:Eukaryotic Initiation Factors; D024243:HMGB1 Protein; C099558:Ki antigen; D008070:Lipopolysaccharides; D018832:Molecular Chaperones; D020543:Proteome; D012333:RNA, Messenger; C036757:lipopolysaccharide B; D046988:Proteasome Endopeptidase Complex