Sec22b is a critical and nonredundant regulator of plasma cell maintenance.
Sec22b is a critical and nonredundant regulator of plasma cell maintenance.
复制标题
DOI：
10.1073/pnas.2213056120
复制
发表时间：
2023-01-10
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管浆细胞在健康和疾病中发挥着核心作用，但浆细胞在产生大量抗体的同时如何持续存在的细胞机制仍然知之甚少。在本文中，我们描述了浆细胞的存活严格依赖于可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体 (SNARE) 分子 Sec22b。我们证明，这种分子是浆细胞内质网和线粒体结构的关键调节剂，如果没有它，体液免疫反应就会被消除。我们的发现对于我们理解抗体介导的免疫具有重要意义，同时也为在病理情况下靶向浆细胞开辟了途径。尽管浆细胞在健康和疾病中发挥着重要作用，但控制其生存和分泌能力的细胞机制仍然知之甚少。在这里，我们确定可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体 (SNARE) Sec22b 是浆细胞维持和功能的独特且关键的调节剂。在没有 Sec22b 的情况下，几乎检测不到浆细胞，并且血清抗体滴度显着降低。因此，Sec22b 缺陷的小鼠无法产生保护性免疫反应。在机制水平上，我们证明了 Sec22b 有助于有效的抗体分泌，并且通过调节浆细胞的转录特性以及内质网和线粒体的形态来维持浆细胞的中心调节因子。总而言之，我们的结果揭示了 Sec22b 作为浆细胞适应性和体液免疫反应调节剂的重要且非多余的作用。
Despite their central role in health and disease, the cellular mechanisms underlying how plasma cells persist while producing large quantities of antibodies are still poorly understood. In this paper, we describe that plasma cell survival is under the strict dependency of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) molecule Sec22b. We showed that this molecule is a key regulator of endoplasmic reticulum and mitochondrial structure in plasma cells, and in its absence, the humoral immune response is abrogated. Our findings have important implications for our understanding of antibody-mediated immunity but also open avenues for targeting plasma cells in pathological contexts. 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.
登录
查看更多内容
影响因子：
10.1
作者：
Karampini E;Bürgisser PE;Olins J;Mulder AA;Jost CR;Geerts D;Voorberg J;Bierings R
通讯作者：
Bierings R
DOI：
10.1084/jem.20170229
发表时间：
2017-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Alloatti A;Rookhuizen DC;Joannas L;Carpier JM;Iborra S;Magalhaes JG;Yatim N;Kozik P;Sancho D;Albert ML;Amigorena S
通讯作者：
Amigorena S
影响因子：
5.5
作者：
Kirk, Semra J.;Cliff, Jacqueline M.;Ward, Theresa H.
通讯作者：
Ward, Theresa H.
DOI：
10.1007/978-1-0716-1425-9_8
发表时间：
2021-01-01
期刊：
BONE MARROW ENVIRONMENT
影响因子：
--
作者：
Bonaud, Amelie;Balabanian, Karl;Espeli, Marion
通讯作者：
Espeli, Marion
DOI：
10.1073/pnas.220247197
发表时间：
2000-11-07
影响因子：
11.1
作者：
Brewer, JW;Diehl, JA
通讯作者：
Diehl, JA