Bonaud, A. orcid.org/0000-0002-4153-9171, Gargowitsch, L., Gilbert, S.M. et al. (22 more authors) (2023) Sec22b is a critical and nonredundant regulator of plasma cell maintenance. Proceedings of the National Academy of Sciences, 120 (2). e2213056120. ISSN 0027-8424
Abstract
Despite the essential role of plasma cells in health and disease, the cellular mechanisms controlling their survival and secretory capacity are still poorly understood. Here, we identified the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Sec22b as a unique and critical regulator of plasma cell maintenance and function. In the absence of Sec22b, plasma cells were hardly detectable and serum antibody titers were dramatically reduced. Accordingly, Sec22b-deficient mice fail to mount a protective immune response. At the mechanistic level, we demonstrated that Sec22b contributes to efficient antibody secretion and is a central regulator of plasma cell maintenance through the regulation of their transcriptional identity and of the morphology of the endoplasmic reticulum and mitochondria. Altogether, our results unveil an essential and nonredundant role for Sec22b as a regulator of plasma cell fitness and of the humoral immune response.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Keywords: | SNARE; antibody; endoplasmic reticulum; mitochondria; plasma cell; Mice; Animals; Plasma Cells; R-SNARE Proteins; SNARE Proteins; Endoplasmic Reticulum; Biological Transport |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/L022389/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 May 2023 15:07 |
Last Modified: | 04 May 2023 15:07 |
Published Version: | http://dx.doi.org/10.1073/pnas.2213056120 |
Status: | Published |
Publisher: | Proceedings of the National Academy of Sciences |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.2213056120 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:198741 |