Progressively impaired proteasomal capacity during terminal plasma cell differentiation

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

Research output: Contribution to journalArticle

107 Citations (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.

Original languageEnglish
Pages (from-to)1104-1113
Number of pages10
JournalEMBO Journal
Volume25
Issue number5
DOIs
Publication statusPublished - Mar 8 2006

Fingerprint

Plasma Cells
Cell Differentiation
Plasmas
Proteasome Inhibitors
Immunoglobulins
Immunoglobulin Subunits
Ubiquitinated Proteins
Apoptosis
Intrinsic Factor
Cell death
Humoral Immunity
Antibody Formation
Cell Death
Stabilization
Antibodies
Substrates
Proteins

Keywords

  • Apoptosis
  • Myeloma
  • Plasma cell
  • Proteasome
  • Unfolded protein response

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Progressively impaired proteasomal capacity during terminal plasma cell differentiation. / Cenci, Simone; Mezghrani, Alexandre; Cascio, Paolo; Bianchi, Giada; Cerruti, Fulvia; Fra, Anna; Lelouard, Hugues; Masciarelli, Silvia; Mattioli, Laura; Oliva, Laura; Orsi, Andrea; Pasqualetto, Elena; Pierre, Philippe; Ruffato, Elena; Tagliavacca, Luigina; Sitia, Roberto.

In: EMBO Journal, Vol. 25, No. 5, 08.03.2006, p. 1104-1113.

Research output: Contribution to journalArticle

Cenci, S, Mezghrani, A, Cascio, P, Bianchi, G, Cerruti, F, Fra, A, Lelouard, H, Masciarelli, S, Mattioli, L, Oliva, L, Orsi, A, Pasqualetto, E, Pierre, P, Ruffato, E, Tagliavacca, L & Sitia, R 2006, 'Progressively impaired proteasomal capacity during terminal plasma cell differentiation', EMBO Journal, vol. 25, no. 5, pp. 1104-1113. https://doi.org/10.1038/sj.emboj.7601009
Cenci, Simone ; Mezghrani, Alexandre ; Cascio, Paolo ; Bianchi, Giada ; Cerruti, Fulvia ; Fra, Anna ; Lelouard, Hugues ; Masciarelli, Silvia ; Mattioli, Laura ; Oliva, Laura ; Orsi, Andrea ; Pasqualetto, Elena ; Pierre, Philippe ; Ruffato, Elena ; Tagliavacca, Luigina ; Sitia, Roberto. / Progressively impaired proteasomal capacity during terminal plasma cell differentiation. In: EMBO Journal. 2006 ; Vol. 25, No. 5. pp. 1104-1113.
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