Sec22b is a critical and nonredundant regulator of plasma cell maintenance
Amélie Bonaud, Laetitia Gargowitsch, Simon Gilbert, Elanchezhian Rajan, Pablo Canales-Herrerías, Daniel Stockholm, Nabila Rahman, Mark O. Collins, Hakan Taskiran, Danika L. Hill, Andrés Alloatti, Nagham Alouche, Stéphanie Balor, Vanessa Soldan, Daniel Gillet, Julien Barbier, Françoise Bachelerie, Kenneth G. C. Smith, Julia Jellusova, Pierre Bruhns, Sebastián Amigorena, Karl Balabanian, Michelle A. Linterman, Andrew A. Peden, Marion Espéli
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.