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Complexin 2 regulates secretion of immunoglobulin in antibody‐secreting cells
Immunity Inflammation and Disease Pub Date : 2019-11-06 , DOI: 10.1002/iid3.276
Emi Tsuru 1 , Kohei Oryu 1 , Ken Sawada 2 , Makoto Nishihara 3 , Masayuki Tsuda 1
Affiliation  

AbstractIntroductionComplexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane. Although much is known about CPLX function in neuronal synaptic vesicle exocytosis, their distribution and role in immune cells are still unclear. In this study, we investigated CPLX2 knockout (KO) mice to reveal the role of CPLXs in exocytosis of lymphocytes.MethodsWe examined the expression of CPLXs and SNAREs in lymphocytes. To study the effect of CPLXs on the immune system in vivo, we analyzed the immune phenotype of CPLX2 KO mice. Furthermore, antibodies secretion from the peritoneal cavity, spleen, and bone marrow cells of wild‐type (WT) and CPLX2 KO mice were determined.ResultsCPLX2 was detected in B cells but not in T cells, while other CPLXs and SNAREs were expressed at a similar level in both B and T cells. To clarify the function of CPLX2 in B lymphocytes, serum concentrations of immunoglobulin G (IgG), IgA, IgM, and IgE were measured in WT and CPLX2 KO mice using enzyme‐linked immunosorbent assay. The level of IgM, which mainly consists of natural antibodies, was higher in KO mice than that in WT mice, while the levels of other antibodies were similar in both types of mice. Additionally, we found that spontaneous secretion of IgM and IgG1 was enhanced from the splenic antibody‐secreting cells (ASCs) of CPLX2 KO mice.ConclusionOur data suggest that CPLX2 inhibits spontaneous secretion of IgM and IgG1 from splenic ASCs. This study provides new insight into the mechanism of antibody secretion of ASCs.

中文翻译:

复合蛋白 2 调节抗体分泌细胞中免疫球蛋白的分泌

摘要介绍复合蛋白 (CPLX) 最初在神经元突触前末梢中发现,是与可溶性蛋白质相互作用的细胞质蛋白。‐乙基马来酰亚胺敏感因子附着蛋白受体(SNARE)复合物调节囊泡与质膜的融合。尽管人们对 CPLX 在神经元突触小泡胞吐作用中的功能了解很多,但它们在免疫细胞中的分布和作用仍不清楚。在本研究中,我们研究了 CPLX2 敲除 (KO) 小鼠,以揭示 CPLX 在淋巴细胞胞吐作用中的作用。方法我们检查了淋巴细胞中 CPLX 和 SNARE 的表达。为了研究 CPLX 对体内免疫系统的影响,我们分析了 CPLX2 KO 小鼠的免疫表型。此外,还测定了野生型(WT)和 CPLX2 KO 小鼠腹膜腔、脾脏和骨髓细胞的抗体分泌。结果CPLX2 在 B 细胞中检测到,但在 T 细胞中未检测到,而其他 CPLX 和 SNARE 在 B 和 T 细胞中都以相似的水平表达。为了阐明 CPLX2 在 B 淋巴细胞中的功能,使用酶联免疫吸附测定法测量 WT 和 CPLX2 KO 小鼠中免疫球蛋白 G (IgG)、IgA、IgM 和 IgE 的血清浓度。IgM主要由天然抗体组成,KO小鼠的IgM水平高于WT小鼠,而两种小鼠的其他抗体水平相似。此外,我们发现 CPLX2 KO 小鼠脾脏抗体分泌细胞 (ASC) 的 IgM 和 IgG1 自发分泌增强。结论我们的数据表明 CPLX2 抑制脾 ASC 自发分泌 IgM 和 IgG1。这项研究为ASC分泌抗体的机制提供了新的见解。
更新日期:2019-11-06
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