Managing and exploiting stress in the antibody factory

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Like us, our cells have evolved strategies to cope with, and sometimes utilize, stress. Molecular analyses of plasma cell biogenesis, lifestyle and death suggest that protein synthesis-dependent stress is utilised to integrate differentiation, function and lifespan control. Plasma cells are short-lived professional secretory cells, each of them capable of releasing several thousands antibodies per second. Their differentiation from B lymphocytes entails the spectacular enlargement of the endoplasmic reticulum (ER), finalized to sustain massive Ig production. Nonetheless, symptoms of ER stress are evident, and the UPR-related transcription factor XBP-1 is essential for differentiation. Surprisingly, the development of such an efficient factory is matched by a decrease in proteasomes. The unbalanced load/capacity ratio leads to accumulation of polyubiquitinated molecules and predisposes plasma cells to apoptosis. Exuberant antibody secretion imposes considerable stress on metabolic and redox homeostasis. Collectively, these stressful conditions may link plasma cell death to antibody production, providing a molecular counter for secreted molecules, as well as an explanation for the peculiar sensitivity of myeloma cells towards proteasome inhibitors.

Original languageEnglish
Pages (from-to)3652-3657
Number of pages6
JournalFEBS Letters
Volume581
Issue number19
DOIs
Publication statusPublished - Jul 31 2007

Fingerprint

Plasma Cells
Industrial plants
Plasmas
Antibodies
Proteasome Inhibitors
Molecules
Endoplasmic Reticulum Stress
Lymphocytes
Cell death
Proteasome Endopeptidase Complex
Endoplasmic Reticulum
Oxidation-Reduction
Antibody Formation
Life Style
Homeostasis
B-Lymphocytes
Cell Death
Transcription Factors
Apoptosis
Proteins

Keywords

  • Antibody secretion
  • Differentiation
  • Plasma cell
  • Proteasomes
  • Protein synthesis and degradation
  • Redox
  • Stress

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Managing and exploiting stress in the antibody factory. / Cenci, Simone; Sitia, Roberto.

In: FEBS Letters, Vol. 581, No. 19, 31.07.2007, p. 3652-3657.

Research output: Contribution to journalArticle

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