Plasma cell maintenance and antibody secretion are under the control of Sec22b-mediated regulation of organelle dynamics
Plasma cell maintenance and antibody secretion are under the control of Sec22b-mediated regulation of organelle dynamics
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DOI：
10.1101/2022.01.14.476154
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发表时间：
2022-01
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通讯作者：
A. Bonaud;Laetitia Gargowitsch;S. Gilbert;E. Rajan;Pablo Canales Herrerias;D. Stockholm;Nabila Rahman;M. Collins;D. Hill;Andrés Alloatti;Nagham Alouche;Stéphanie Balor;Vanessa Soldan;D. Gillet;J. Barbier;F. Bachelerie;Kenneth G. C. Smith;P. Bruhns;S. Amigorena;K. Balabanian;M. Linterman;A. Peden;M. Espéli
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作者：
A. Bonaud;Laetitia Gargowitsch;S. Gilbert;E. Rajan;Pablo Canales Herrerias;D. Stockholm;Nabila Rahman;M. Collins;D. Hill;Andrés Alloatti;Nagham Alouche;Stéphanie Balor;Vanessa Soldan;D. Gillet;J. Barbier;F. Bachelerie;Kenneth G. C. Smith;P. Bruhns;S. Amigorena;K. Balabanian;M. Linterman;A. Peden;M. Espéli
尽管浆细胞在健康和疾病中扮演着重要的角色，但控制其存活和分泌能力的细胞机制仍然知之甚少。在这里，我们确定SNARE Sec22b是浆细胞维持和功能的独特和关键的调节因子。在没有Sec22b的情况下，几乎检测不到浆细胞，血清抗体效价显著降低。因此，Sec22b缺陷小鼠无法产生保护性免疫反应。在机制水平上，我们通过调节内质网和线粒体的形态，证明了Sec22b对于有效的抗体分泌以及浆细胞的适合性是必不可少的。总之，我们的结果揭示了Sec22b通过控制细胞器动力学来调节浆细胞生物学的关键作用。
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 SNARE Sec22b as a unique and critical regulator of plasma cell maintenance and function. In absence of Sec22b, plasma cells were barely 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 is indispensable for efficient antibody secretion but also for plasma cell fitness through the regulation of the morphology of the endoplasmic reticulum and mitochondria. Altogether, our results unveil a critical role for Sec22b-mediated regulation of plasma cell biology through the control of organelle dynamics.