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 language | English |
|---|---|
| Pages (from-to) | 1104-1113 |
| Number of pages | 10 |
| Journal | EMBO Journal |
| Volume | 25 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 8 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Progressively impaired proteasomal capacity during terminal plasma cell differentiation
AU - Cenci, Simone
AU - Mezghrani, Alexandre
AU - Cascio, Paolo
AU - Bianchi, Giada
AU - Cerruti, Fulvia
AU - Fra, Anna
AU - Lelouard, Hugues
AU - Masciarelli, Silvia
AU - Mattioli, Laura
AU - Oliva, Laura
AU - Orsi, Andrea
AU - Pasqualetto, Elena
AU - Pierre, Philippe
AU - Ruffato, Elena
AU - Tagliavacca, Luigina
AU - Sitia, Roberto
PY - 2006/3/8
Y1 - 2006/3/8
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Myeloma
KW - Plasma cell
KW - Proteasome
KW - Unfolded protein response
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UR - http://www.scopus.com/inward/citedby.url?scp=33644871448&partnerID=8YFLogxK
U2 - 10.1038/sj.emboj.7601009
DO - 10.1038/sj.emboj.7601009
M3 - Article
C2 - 16498407
AN - SCOPUS:33644871448
VL - 25
SP - 1104
EP - 1113
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 5
ER -