Sec22b is a critical and nonredundant regulator of plasma cell maintenance

Bonaud, Amélie, Gargowitsch, Laetitia, Gilbert, Simon M., Rajan, Elanchezhian, Canales-Herrerias, Pablo, Stockholm, Daniel, Rahman, Nabila F., Collins, Mark O., Taskiran, Hakan, Hill, Danika L., Alloatti, Andres, Alouche, Nagham, Balor, Stéphanie, Soldan, Vanessa, Gillet, Daniel, Barbier, Julien, Bachelerie, Françoise, Smith, Kenneth G. C., Jellusova, Julia, Bruhns, Pierre, Amigorena, Sebastian, Balabanian, Karl, Linterman, Michelle A., Peden, Andrew A. and Espéli, Marion 2023. Sec22b is a critical and nonredundant regulator of plasma cell maintenance. Proceedings of the National Academy of Sciences of the United States of America 120 (2) , e2213056120. 10.1073/pnas.2213056120

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Date of First Compliant Deposit:	30 April 2024
Last Modified:	30 Apr 2024 13:15
URI:	https://orca.cardiff.ac.uk/id/eprint/168510

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