TY - JOUR
T1 - Sec22b is a critical and nonredundant regulator of plasma cell maintenance
AU - Bonaud, Amélie
AU - Gargowitsch, Laetitia
AU - Gilbert, Simon M.
AU - Rajan, Elanchezhian
AU - Canales-Herrerias, Pablo
AU - Stockholm, Daniel
AU - Rahman, Nabila F.
AU - Collins, Mark O.
AU - Taskiran, Hakan
AU - Hill, Danika L.
AU - Alloatti, Andres
AU - Alouche, Nagham
AU - Balor, Stéphanie
AU - Soldan, Vanessa
AU - Gillet, Daniel
AU - Barbier, Julien
AU - Bachelerie, Françoise
AU - Smith, Kenneth G.C.
AU - Jellusova, Julia
AU - Bruhns, Pierre
AU - Amigorena, Sebastian
AU - Balabanian, Karl
AU - Linterman, Michelle A.
AU - Peden, Andrew A.
AU - Espéli, Marion
N1 - Funding Information:
We thank Dr. N. Setterblad, C. Doliger, and S. Duchez (Plateforme technologique IRSL, Paris, France), Dr. V. Parietti (Mouse facility IRSL, Paris, France), S. Guibert (IntegraGen), M. Khamyath, and V. Gourhand for their technical assistance. We are grateful to Pr. A. Toubert for his comments on this manuscript. The study was supported by the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LabEx LERMIT) (M.E. and K.B.); an ANR JCJC grant (ANR-19-CE15-0019-01), an ANR @RAction grant (ANR-14-ACHN-0008), a “Fondation ARC pour la recherche sur le cancer” grant (P JA20181208173), and a grant from IdEx Université Paris-Cité (ANR-18-IDEX-0001) to M.E.; and an ANR PRC grant (ANR-17-CE14-0019) and an INCa grant (PRT-K 2017) to K.B. P.B. acknowledges funding from the French National Research Agency grant ANR-18-CE15-0001 project Autoimmuni-B, by the Institut Carnot Pasteur Microbes et Santé grant ANR-11-CARN-0017-01, the Institut Pasteur, and the Institut National de la Santé et de la Recherche Médicale (INSERM). M.A.L. is supported by Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0427, BBS/E/B/000C0428, and the Campus Capability Core Grant to the Babraham Institute). A.A.P. and M.O.C. were supported by a grant from the Biotechnology and Biological Sciences Research Council (BB/L022389/1). D.L.H. is supported by a National Health and Medical Research Council Australia Early-Career Fellowship (APP1139911). N.A. was supported by a PhD fellowship from the French Ministry for education and by a fourth year PhD fellowship from the “Fondation ARC pour la recherche sur le cancer.” P.C.-H. was supported partly by a stipend from the Pasteur-Paris University (PPU) International PhD program, and by a fellowship from the French Fondation pour la Recherche Médicale (FRM). K.G.C.S. was supported by the Wellcome Trust (Programme Grant Number 083650/Z/07/Z). J.J’s research is supported by the German Research Foundation project number: 419193696 and through the CRC1335. H.T. is supported through the graduate school of the Max Planck Institute for Immunobiology and Epigenetics (IMPRS-IE) and through the CRC1335. The "EMiLy" U1160 INSERM unit is a member of the OPALE Carnot institute, The Organization for Partnerships in Leukemia (Institut Carnot OPALE, Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Paris, France. Web: www.opale.org. Email: [email protected]).
Funding Information:
ACKNOWLEDGMENTS. We thank Dr. N. Setterblad, C. Doliger, and S. Duchez (Plateforme technologique IRSL, Paris, France), Dr. V. Parietti (Mouse facility IRSL, Paris, France), S. Guibert (IntegraGen), M. Khamyath, and V. Gourhand for their technical assistance. We are grateful to Pr. A. Toubert for his comments on this manuscript. The study was supported by the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LabEx LERMIT) (M.E. and K.B.); an ANR JCJC grant (ANR-19-CE15-0019-01), an ANR @RAction
Funding Information:
grant (ANR-14-ACHN-0008),a “Fondation ARC pour la recherche sur le cancer” grant (P JA20181208173), and a grant from IdEx Université Paris-Cité (ANR-18-IDEX-0001) to M.E.; and an ANR PRC grant (ANR-17-CE14-0019) and an INCa grant (PRT-K 2017) to K.B. P.B. acknowledges funding from the French National Research Agency grant ANR-18-CE15-0001 project Autoimmuni-B, by the Institut Carnot Pasteur Microbes et Santé grant ANR-11-CARN-0017-01, the Institut Pasteur, and the Institut National de la Santé et de la Recherche Médicale (INSERM). M.A.L. is supported by Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0427, BBS/E/B/000C0428, and the Campus Capability Core Grant to the Babraham Institute). A.A.P. and M.O.C. were supported by a grant from the Biotechnology and Biological Sciences Research Council (BB/L022389/1). D.L.H. is supported by a National Health and Medical Research Council Australia Early-Career Fellowship (APP1139911). N.A. was supported by a PhD fellowship from the French Ministry for education and by a fourth year PhD fellowship from the “Fondation ARC pour la recherche sur le cancer.” P.C.-H. was supported partly by a stipend from the Pasteur-Paris University (PPU) International PhD program, and by a fellowship from the French Fondation pour la Recherche Médicale (FRM). K.G.C.S. was supported by the Wellcome Trust (Programme Grant Number 083650/Z/07/Z). J.J’s research is supported by the German Research Foundation project number: 419193696 and through the CRC1335. H.T. is supported through the graduate school of the Max Planck Institute for Immunobiology and Epigenetics (IMPRS-IE) and through the CRC1335. The "EMiLy" U1160 INSERM unit is a member of the
Publisher Copyright:
Copyright © 2023 the Author(s).
PY - 2023/1/10
Y1 - 2023/1/10
N2 - 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.
AB - 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.
KW - antibody
KW - endoplasmic reticulum
KW - mitochondria
KW - plasma cell
KW - SNARE
UR - http://www.scopus.com/inward/record.url?scp=85145428908&partnerID=8YFLogxK
U2 - 10.1073/pnas.2213056120
DO - 10.1073/pnas.2213056120
M3 - Article
C2 - 36595686
AN - SCOPUS:85145428908
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 2
M1 - e2213056120
ER -