Sec22b is a critical and non-redundant regulator of plasma cell maintenance

Amélie Bonaud (1, 2, 3) , Laetitia Gargowitsch (4) , Simon M Gilbert (5) , Elanchezhian Rajan (6) , Pablo Canales-Herrerias (7) , Daniel Stockholm (8, 9) , Nabila F Rahman (10) , Mark O Collins (6) , Hakan Taskiran (11, 12) , Danika L Hill (13, 14) , Andres Alloatti (15, 16) , Nagham Alouche (4) , Stéphanie Balor (17) , Vanessa Soldan (17) , Daniel Gillet (18) , Julien Barbier (18) , Françoise Bachelerie (4) , Kenneth G C Smith (5) , Julia Jellusova (11) , Pierre Bruhns (7) , Sebastian Amigorena (15) , Karl Balabanian (1, 2, 3) , Michelle A Linterman (13) , Andrew A Peden (6) , Marion Espéli (1, 2, 3)

1 IRSL - Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH)
2 CNRS GDR 3697 Micronit - Microenvironnement des niches tumorales
3 AP-HP - Hopital Saint-Louis [AP-HP]
4 MI2 - Inflammation, microbiome, immunosurveillance
5 CAM - University of Cambridge [UK]
6 University of Sheffield [Sheffield]
7 Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology
8 EPHE - École Pratique des Hautes Études
9 CRSA - Centre de Recherche Saint-Antoine
10 Cardiff University
11 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
12 MPI-IE - Max Planck Institute of Immunobiology and Epigenetics
13 The Babraham Institute [Cambridge, UK]
14 Monash University [Melbourne]
15 U932 - Immunité et cancer
16 Universidad Nacional de Rosario [Santa Fe]
17 CBI - Centre de Biologie Intégrative
18 SIMoS - Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO)

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 absence of Sec22b, plasma cells were hardly detectable and serum antibody titres 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 non-redundant role for Sec22b as a regulator of plasma cell fitness and of the humoral immune response.

Mots clés: plasma cell; SNARE; antibody; endoplasmic reticulum; mitochondria

Domaines: Sciences du Vivant [q-bio]

Amélie Bonaud, Laetitia Gargowitsch, Simon M Gilbert, Elanchezhian Rajan, Pablo Canales-Herrerias, et al.. Sec22b is a critical and non-redundant regulator of plasma cell maintenance. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 (2), pp.e2213056120. ⟨10.1073/pnas.2213056120⟩. ⟨hal-04064289v2⟩