B-to plasma-cell terminal differentiation entails oxidative stress and profound reshaping of the antioxidant responses

Silvia Masciarelli, Milena Bertolotti, Sun Hee Yim, Jose M. Garcia-Manteiga, Yoo-Jin Kim, Min-Hee Kang, Yoshihito Iuchi, Junichi Fujii, Roberta Vené, Anna Rubartelli, Sue Goo Rhee, Roberto Sitia

Risultato della ricerca: Contributo in rivistaArticolo in rivista

63 Citazioni (Scopus)

Abstract

Limited amounts of reactive oxygen species are necessary for cell survival and signaling, but their excess causes oxidative stress. H2O 2 and other reactive oxygen species are formed as byproducts of several metabolic pathways, possibly including oxidative protein folding in the endoplasmic reticulum. B-to plasma-cell differentiation is characterized by a massive expansion of the endoplasmic reticulum, finalized to sustain abundant immunoglobulin (Ig) synthesis and secretion. The increased production of disulfide-rich Ig might cause oxidative stress that could serve signaling roles in the differentiation and lifespan control of antibody-secreting cells. Here we show that terminal B-cell differentiation entails redox stress, NF-E2-related factor-2 (Nrf2) activation, and reshaping of the antioxidant responses. However, plasma-cell differentiation was not dramatically impaired in peroxiredoxin (Prx)1-, 2-, 3-, and 4-, glutathione peroxidase 1-, and Nrf2-knockout splenocytes, suggesting redundancy and robustness in antioxidant systems. Endoplasmic reticulum (ER)-resident Prx4 increases dramatically during differentiation. In its absence, IgM secretion was not significantly affected, but more high-molecular-weight covalent complexes accumulated intracellularly. Our results suggest that the early intracellular production of H 2O2 facilitates B-cell proliferation and reveal a role for the Nrf2 pathway in the differentiation and function of IgM-secreting cells. © 2010, Mary Ann Liebert, Inc.
Lingua originaleEnglish
pagine (da-a)1133-1144
Numero di pagine12
RivistaANTIOXIDANTS & REDOX SIGNALING
Volume13
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Animals
  • Antioxidants
  • B-Lymphocytes
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Endoplasmic Reticulum
  • Immunoglobulin M
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2
  • Oxidation-Reduction
  • Oxidative Stress
  • Plasma Cells
  • Reactive Oxygen Species
  • Signal Transduction

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