Rialland Pascale, Lankar Danielle, Raposo Graça, Bonnerot Christian, Hubert Pascale
INSERM U520, Institut Curie, 26, rue d'Ulm, 75 248 Paris cedex 05, France.
Biol Cell. 2006 Aug;98(8):491-501. doi: 10.1042/BC20060027.
Exosomes are small membrane vesicles secreted by several cell types during exocytic fusion of multivesicular bodies with the plasma membrane. Exosomes from tumour cells can transfer antigens from cell to cell, a property favouring antigen-specific immune responses in vitro and in vivo, and are thus an interesting putative therapeutic tool in human cancers. Exosomes have been well studied in EBV (Epstein-Barr virus)-transformed human B-cell lines; however, biological stimuli regulating exosome secretion quantitatively and/or qualitatively still remain poorly defined.
We analysed the effect of the BCR stimulation on exosome release in the human follicular lymphoma B-cell line DOHH2. We found that BCR (B-cell receptor) triggering of DOHH2 cells induced the polarization of CD63(+) MHC class II compartments. Moreover, BCR stimulation increased the release of exosome-associated proteins in the extracellular space. Finally, we found that the BCR was expressed at the surface of exosomes, and could target a bound anti-human IgG to these vesicles.
BCR can modulate the protein content of exosomes upon stimulation, and can target its bound antigen to these vesicles.
外泌体是多泡体与质膜进行胞吐融合过程中由多种细胞类型分泌的小膜泡。肿瘤细胞来源的外泌体能够在细胞间传递抗原,这一特性在体外和体内均有利于抗原特异性免疫反应,因此是一种在人类癌症治疗中颇具潜力的治疗工具。外泌体在EB病毒(Epstein-Barr virus)转化的人B细胞系中已得到充分研究;然而,定量和/或定性调节外泌体分泌的生物刺激因素仍未明确。
我们分析了B细胞受体(BCR)刺激对人滤泡性淋巴瘤B细胞系DOHH2中外泌体释放的影响。我们发现,DOHH2细胞的BCR激活诱导了CD63(+) Ⅱ类主要组织相容性复合体区室的极化。此外,BCR刺激增加了细胞外空间中外泌体相关蛋白的释放。最后,我们发现BCR在外泌体表面表达,并能将结合的抗人IgG靶向到这些囊泡上。
BCR刺激后可调节外泌体的蛋白质含量,并能将其结合的抗原靶向到这些囊泡上。