The FKBP7 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from the Raji B-lymphocyte cell line, featuring targeted disruption of the FKBP7 gene. This heterogeneous knockout pool enables loss-of-function studies without clonal selection bias, preserving population diversity for robust phenotypic analysis. The polyclonal format is especially suited for investigating FKBP7-dependent endoplasmic reticulum (ER) proteostasis pathways in a biologically relevant lymphoma context.
The Raji cell line is an Epstein-Barr virus (EBV)-positive, suspension-adapted B lymphocyte model derived from a Burkitt’s lymphoma patient. These cells are widely employed in B-cell lymphoma research due to their high proliferative capacity and retention of B-cell receptor signaling and immunoglobulin secretion. Their EBV-transformed lymphoblastoid nature provides a convenient and reproducible system for studying ER stress responses and secretory pathway dynamics, making them an ideal host for FKBP7 knockout studies.
FKBP7 encodes an ER-resident peptidyl-prolyl isomerase that functions as a chaperone in protein folding and quality control, physically interacting with BiP (GRP78), calnexin, calreticulin, HSP90B1, and PDIA3. Its expression is induced by ER stress triggers such as tunicamycin and thapsigargin, acting downstream of transcription factors ATF4 and XBP1. FKBP7 loss disrupts ER homeostasis, leading to constitutive activation of the unfolded protein response (UPR). This includes PERK (EIF2AK3)-dependent phosphorylation of eIF2??, IRE1 (ERN1)-mediated XBP1 mRNA splicing, and ATF6 processing, which collectively upregulate CHOP (DDIT3) and other UPR target genes. Through its client interactions, FKBP7 influences folding of secretory proteins including immunoglobulins, linking its chaperone activity to B-cell effector functions.
In Raji B cells, FKBP7 knockout exacerbates basal ER stress and sensitizes cells to ER stress-induced apoptosis, while potentially impairing immunoglobulin folding and secretion. This phenotype mirrors key aspects of B-cell malignancies where proteostatic imbalance contributes to pathogenesis. The constitutive UPR activation provides a platform to identify vulnerabilities exploitable for therapeutic intervention, such as synthetic lethal combinations with proteasome inhibitors or ER stressors. Consequently, this model is particularly valuable for neurodegenerative disease research and ER stress-related disorders, offering insights into how transformed lymphocytes cope with chronic ER stress.
These polyclonal knockout cells are optimized for a variety of assays, including Western blot detection of UPR markers (BiP, CHOP, phospho-eIF2??), RT-qPCR analysis of XBP1 mRNA splicing, and flow cytometry with Annexin V/PI to quantify apoptosis. Researchers can leverage this model for high-throughput screening of proteostasis modulators, drug sensitivity profiling with ER stressors (tunicamycin, thapsigargin), and immunofluorescence imaging of ER morphology. The FKBP7 knockout system also facilitates investigation of B-cell receptor biogenesis and validation of FKBP7 as a therapeutic target in lymphoma and multiple myeloma. For further technical specifications, please contact Ascent Research.
