The OSBPL6 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the OSBPL6 gene in the human Raji B lymphocyte line. This loss-of-function model enables dissection of OSBPL6-dependent lipid transport processes in a hematopoietic background. The polyclonal format avoids clonal selection bias, providing a genetically diverse population for robust functional analyses of sterol-sensing pathways and membrane contact site biology in B cells.
Raji cells, derived from a Burkitt’s lymphoma patient, serve as a well-established B-cell model for lymphoma and immune signaling. Their B lymphocyte characteristics, including surface immunoglobulin receptors and rapid proliferation, facilitate investigation of how lipid dynamics modulate oncogenic processes and B-cell receptor (BCR) signal transduction.
OSBPL6 (oxysterol-binding protein-like 6) functions at endoplasmic reticulum-organelle membrane contact sites, where it mediates non-vesicular countertransport of phosphatidylinositol 4-phosphate (PI(4)P) and cholesterol. This lipid exchange activity depends on interactions with VAPA and VAPB, which tether the ER to target membranes, and is transcriptionally regulated by SREBP factors and liver X receptor in response to intracellular sterol levels. Downstream, knockout of OSBPL6 disrupts cholesterol trafficking, alters PI(4)P metabolism, and attenuates mTORC1 signaling, thereby impairing lipid homeostasis and anabolic growth programs.
In the Raji B-cell context, cholesterol-rich membrane microdomains are critical for BCR-mediated proliferation and survival. Disruption of OSBPL6-mediated cholesterol delivery perturbs plasma membrane lipid order and likely impairs mTORC1 activation, providing a model to dissect the crosstalk between lipid metabolism and oncogenic signaling in Burkitt’s lymphoma and other B-cell malignancies.
Research applications include lipidomic profiling to map altered phospholipid species, filipin staining for cholesterol localization, fluorescence microscopy to visualize organelle contact sites, phospho-mTORC1 assays to gauge nutrient sensing, and flow cytometry for proliferation and activation markers. Co-immunoprecipitation with VAPA/VAPB assesses complex integrity. The model further supports drug screening for metabolic disorders, hypercholesterolemia, and hematologic cancers. For additional technical information, please contact Ascent Research.
