Identification of soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic machinery in human plasma cells:: SNAP-23 is essential for antibody secretion
Identification of soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic machinery in human plasma cells:: SNAP-23 is essential for antibody secretion
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DOI：
10.4049/jimmunol.175.10.6686
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发表时间：
2005-11-15
影响因子：
4.4
通讯作者：
Campos-Caro, A
中科院分区：
文献类型：
--
作者：
Reales, E;Mora-López, F;Campos-Caro, A
浆细胞（PC）是在有丝分裂后状态终末分化的B淋巴细胞，具有制造和输出Ig的独特目的。尽管这一过程在脊椎动物的生存中很重要，但还没有研究来了解PC调节IG胞吐的分子事件。本研究探讨了可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）系统在人类PC中的可能存在，并检查其在IG分泌中的功能作用。从肠固有层和血液中获得的正常人PC以及人PC系中可以容易地检测到Syntaxin-2、Syntaxin-3、Syntaxin-4、囊泡相关膜蛋白（VAMP）-2、VAMP-3和突触体相关蛋白（SNAP）-23。由于SNAP-23在SNARE复合物形成中起核心作用，因此选择它来检查SNARE系统在PC IG分泌中的可能功能影响。当将重组SNAP-23融合蛋白导入细胞中时，在PC系的培养上清液中观察到IG产生的完全消除，以及在正常PC的培养上清液中观察到。这些结果提供了见解，第一次，到人PC IG分泌的组成性囊泡运输的分子机制，并提出证据表明，至少SNAP-23是必不可少的抗体生产。
Plasma cells (PC) are B-lymphocytes terminally differentiated in a postmitotic state, with the unique purpose of manufacturing and exporting Igs. Despite the importance of this process in the survival of vertebrates, no studies have been made to understand the molecular events that regulate Ig exocytosis by PC. The present study explores the possible presence of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) system in human PC, and examines its functional role in Ig secretion. Syntaxin-2, Syntaxin-3, Syntaxin-4, vesicle-associated membrane protein (VAMP)-2, VAMP-3, and synaptosome-associated protein (SNAP)-23 could be readily detected in normal human PC obtained from intestinal lamina propria and blood, as well as in human PC lines. Because SNAP-23 plays a central role in SNAREs complex formation, it was chosen to examine possible functional implications of the SNARE system in PC Ig secretion. When recombinant SNAP-23 fusion protein was introduced into the cells, a complete abolishment of Ig production was observed in the culture supernatants of PC lines, as well as in those of normal PC. These results provide insights, for the first time, into the molecular machinery of constitutive vesicular trafficking in human PC Ig secretion and present evidence indicating that at least SNAP-23 is essential for Ab production.