Klimtchuk Elena S, Prokaeva Tatiana B, Spencer Brian H, Gursky Olga, Connors Lawreen H
a Gerry Amyloidosis Research Laboratory, Amyloidosis Center , Boston University School of Medicine , Boston , MA , USA.
b Department of Physiology and Biophysics , Boston University School of Medicine , Boston , MA , USA.
Amyloid. 2017 Jun;24(2):115-122. doi: 10.1080/13506129.2017.1336996. Epub 2017 Jun 20.
Immunoglobulin (Ig) light chain (LC) amyloidosis (AL) is characterized by the overproduction and tissue deposition of monoclonal LC in various organs and tissues. The plasma circulating monoclonal LC is believed to be the precursor of the deposited protein and in vitro studies aimed at understanding AL pathobiology have mainly focused on LC and its variable domain. While 33% of patients have free circulating monoclonal LC, ∼40% feature LC complexed to heavy chain (HC) forming a monoclonal intact Ig; the significance of free vs. bound LC in the amyloid forming pathway is unknown. To address this issue, we developed a cell-based model using stable mouse plasmacytoma Sp2/0 cells that co-express patient-derived amyloidogenic LC and HC proteins. The system was designed using amyloidogenic kappa and lambda LC, and gamma HC sequences; stable production and secretion of either free LC and/or intact Ig were accomplished by varying the LC to HC ratios. This novel cell-based system provides a relevant tool to systematically investigate LC and HC interactions, and the molecular events leading to the development of AL amyloidosis.
免疫球蛋白（Ig）轻链（LC）淀粉样变性（AL）的特征是单克隆LC在各种器官和组织中过度产生并沉积。循环血浆中的单克隆LC被认为是沉积蛋白的前体，旨在了解AL病理生物学的体外研究主要集中在LC及其可变区。虽然33%的患者有游离循环单克隆LC，但约40%的患者的特征是LC与重链（HC）复合形成单克隆完整Ig；游离LC与结合LC在淀粉样形成途径中的意义尚不清楚。为了解决这个问题，我们使用稳定的小鼠浆细胞瘤Sp2/0细胞开发了一种基于细胞的模型，该细胞共表达患者来源的淀粉样生成LC和HC蛋白。该系统使用淀粉样生成κ和λ LC以及γ HC序列进行设计；通过改变LC与HC的比例实现游离LC和/或完整Ig的稳定产生和分泌。这种新型的基于细胞的系统为系统研究LC和HC的相互作用以及导致AL淀粉样变性发展的分子事件提供了一个相关工具。
