Progressively impaired proteasomal capacity during terminal plasma cell differentiation

Silvia Masciarelli, Simone Cenci, Alexandre Mezghrani, Paolo Cascio, Giada Bianchi, Fulvia Cerruti, Anna Fra, Hugues Lelouard, Laura Mattioli, Laura Oliva, Andrea Orsi, Elena Pasqualetto, Philippe Pierre, Elena Ruffato, Luigina Tagliavacca, Roberto Sitia

Risultato della ricerca: Contributo in rivistaArticolo in rivista

116 Citazioni (Scopus)

Abstract

After few days of intense immunoglobulin (Ig) secretion, most plasma cells undergo apoptosis, thus ending the humoral immune response. We asked whether intrinsic factors link plasma cell lifespan to Ig secretion. Here we show that in the late phases of plasmacytic differentiation, when antibody production becomes maximal, proteasomal activity decreases. The excessive load for the reduced proteolytic capacity correlates with accumulation of poly-ubiquitinated proteins, stabilization of endogenous proteasomal substrates (including Xbp1s, IκBα, and Bax), onset of apoptosis, and sensitization to proteasome inhibitors (PI). These events can be reproduced by expressing Ig-μ chain in nonlymphoid cells. Our results suggest that a developmental program links plasma cell death to protein production, and help explaining the peculiar sensitivity of normal and malignant plasma cells to PI. ©2006 European Molecular Biology Organization.
Lingua originaleEnglish
pagine (da-a)1104-1113
Numero di pagine10
RivistaEMBO Journal
Volume25
DOI
Stato di pubblicazionePubblicato - 2006

Keywords

  • Animals
  • Apoptosis
  • Cell Differentiation
  • DNA-Binding Proteins
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • I-kappa B Proteins
  • Immunoglobulin M
  • Immunoglobulin mu-Chains
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloma
  • NF-KappaB Inhibitor alpha
  • Nuclear Proteins
  • Plasma Cells
  • Plasma cell
  • Protease Inhibitors
  • Proteasome
  • Proteasome Inhibitors
  • Regulatory Factor X Transcription Factors
  • Spleen
  • Transcription Factors
  • Ubiquitin
  • Unfolded protein response
  • X-Box Binding Protein 1
  • bcl-2-Associated X Protein

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