CHOP-independent apoptosis and pathway-selective induction of the UPR in developing plasma cells

Silvia Masciarelli, Anna M. Fra, Niccolò Pengo, Milena Bertolotti, Simone Cenci, Claudio Fagioli, David Ron, Linda M. Hendershot, Roberto Sitia

Research output: Contribution to journalArticle

Abstract

Upon antigen stimulation, B lymphocytes differentiate into antibody secreting cells (ASC), most of which undergo apoptosis after a few days of intense Ig production. Differentiation entails expansion of the endoplasmic reticulum (ER) and requires XBP1 but not other elements of the unfolded protein response, like PERK. Moreover, normal and malignant ASC are exquisitely sensitive to proteasome inhibitors, but the underlying mechanisms are poorly understood. Here we analyze the role of C/EBP homologous protein (CHOP), a transcription factor mediating apoptosis in many cell types that experience high levels of ER stress. CHOP is transiently induced early upon B cell stimulation: covalent IgM aggregates form more readily and IgM secretion is slower in chop-/- cells. Despite these subtle changes, ASC differentiation and lifespan are normal in chop-/- mice. Unlike fibroblasts and other cell types, chop-/- ASC are equally or slightly more sensitive to proteasome inhibitors and ER stressors, implying tissue-specific roles for CHOP in differentiation and stress.

Original languageEnglish
Pages (from-to)1356-1365
Number of pages10
JournalMolecular Immunology
Volume47
Issue number6
DOIs
Publication statusPublished - Mar 2010

Keywords

  • ER stress
  • IgM secretion
  • Plasma cell differentiation
  • Proteasome inhibitors
  • UPR

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

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    Masciarelli, S., Fra, A. M., Pengo, N., Bertolotti, M., Cenci, S., Fagioli, C., Ron, D., Hendershot, L. M., & Sitia, R. (2010). CHOP-independent apoptosis and pathway-selective induction of the UPR in developing plasma cells. Molecular Immunology, 47(6), 1356-1365. https://doi.org/10.1016/j.molimm.2009.12.003