The CASP8 Knockout Raji Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal population derived from Raji B lymphocytes, with disruption of the endogenous CASP8 gene. This heterogeneous knockout pool ablates caspase-8 protein function, providing a loss-of-function model for studying extrinsic apoptosis and necroptosis. The polyclonal format avoids single-clone artifacts and is suited for experiments requiring population-level knockout effects.
Raji cells, established from a Burkitt lymphoma patient, are EBV-positive and exhibit an immature B-cell phenotype, widely used to model aggressive B-cell malignancies. Their viral status influences apoptosis and survival pathways, making them a relevant platform for investigating lymphomagenesis and therapeutic resistance. The suspension growth facilitates high-throughput applications.
CASP8 encodes the initiator caspase-8, which mediates death receptor-induced extrinsic apoptosis upon activation by Fas ligand, TNF-??, or TRAIL. Within the DISC, FADD recruits and activates caspase-8, which directly cleaves caspases-3 and -7 and the BID protein, linking to mitochondrial apoptosis. Caspase-8 also suppresses necroptosis by cleaving RIPK1 and RIPK3, preventing MLKL-dependent membrane permeabilization. Additionally, it modulates NF-??B signaling and inflammasome activity through interactions with c-FLIP, TRADD, and TRAF2.
CASP8 knockout in the Raji background abolishes death receptor-mediated apoptosis, conferring resistance to FasL and TRAIL, a hallmark of aggressive lymphomas. It may also impair necroptosis and alter NF-??B-driven transcription, impacting immune responses and lymphomagenesis. This model mimics aspects of autoimmune lymphoproliferative syndrome and immunodeficiency, enabling dissection of caspase-8-dependent and -independent signaling branches.
These polyclonal knockout cells are ideal for investigating apoptosis resistance in B-cell lymphoma, screening for pro-apoptotic compounds, and dissecting necroptosis and NF-??B pathways. Assays include flow cytometry for Annexin V/PI after death ligand treatment, western blotting for caspase-8 and cleaved caspases, cell viability assays with necrostatin-1, and co-immunoprecipitation of DISC components. For technical inquiries, please contact Ascent Research.
