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In vitro co-expression of human amyloidogenic immunoglobulin light and heavy chain proteins: a relevant cell-based model of AL amyloidosis.
- Source :
-
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis [Amyloid] 2017 Jun; Vol. 24 (2), pp. 115-122. Date of Electronic Publication: 2017 Jun 20. - Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Aged
Amyloid genetics
Animals
Female
Humans
Immunoglobulin Heavy Chains genetics
Immunoglobulin Light Chains genetics
Immunoglobulin Light-chain Amyloidosis genetics
Immunoglobulin Light-chain Amyloidosis pathology
Immunoglobulin Variable Region genetics
Male
Mice
Amyloid metabolism
Immunoglobulin Heavy Chains biosynthesis
Immunoglobulin Light Chains biosynthesis
Immunoglobulin Light-chain Amyloidosis metabolism
Immunoglobulin Variable Region biosynthesis
Models, Biological
Subjects
Details
- Language :
- English
- ISSN :
- 1744-2818
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
- Publication Type :
- Academic Journal
- Accession number :
- 28632419
- Full Text :
- https://doi.org/10.1080/13506129.2017.1336996