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.

Bertolotti, M., Yim, S. H., Garcia-manteiga, J. M., Masciarelli, S., Kim, Y. -., Kang, M. -., Iuchi, Y., Fujii, J., Vene, R., Rubartelli, A., Rhee, S. G., Sitia, R., B-to plasma-cell terminal differentiation entails oxidative stress and profound reshaping of the antioxidant responses, <<ANTIOXIDANTS & REDOX SIGNALING>>, 2010; 13 (8): 1133-1144. [doi:10.1089/ars.2009.3079] [http://hdl.handle.net/10807/147555]

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

Masciarelli, S.;
2010

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.
Inglese
Bertolotti, M., Yim, S. H., Garcia-manteiga, J. M., Masciarelli, S., Kim, Y. -., Kang, M. -., Iuchi, Y., Fujii, J., Vene, R., Rubartelli, A., Rhee, S. G., Sitia, R., B-to plasma-cell terminal differentiation entails oxidative stress and profound reshaping of the antioxidant responses, <<ANTIOXIDANTS & REDOX SIGNALING>>, 2010; 13 (8): 1133-1144. [doi:10.1089/ars.2009.3079] [http://hdl.handle.net/10807/147555]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/147555
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