The COMMD2 Knockout Raji Polyclonal Cells represent a polyclonal population of Raji B lymphocytes edited via CRISPR/Cas9 to disrupt the COMMD2 gene. This polyclonal knockout model is supplied as a heterogeneous pool of edited cells, each carrying targeted gene disruptions within the COMMD2 locus, enabling functional studies of COMMD2 in a B-cell context.
The parental Raji cell line was established from a Burkitt lymphoma patient and is Epstein-Barr virus (EBV)-positive. Raji cells are a widely used model for B-cell malignancies, exhibiting characteristics of mature B lymphocytes including robust antibody production, antigen presentation capabilities, and active immune response signaling. Their lymphoblastoid phenotype and well-characterized signaling networks make them particularly suitable for investigating pathways relevant to B-cell lymphomagenesis and immune function.
COMMD2 is a critical negative regulator of NF-??B signaling, promoting ubiquitination and proteasomal degradation of p65 (RELA) to suppress expression of pro-inflammatory genes such as IL-6 and TNF. This function relies on its assembly with COMMD1, CCDC22, CCDC93, and C16orf62 within the CCC complex, which recruits the Cullin 2 ubiquitin ligase to target NF-??B subunits. Upstream signals including TNF-??, IL-1??, and TLR ligands activate COMMD2, while downstream it interacts with copper transporters ATP7A and ATP7B to facilitate copper export. Thus, COMMD2 integrates inflammatory and metal homeostatic pathways, with its disruption leading to elevated NF-??B activity and impaired copper trafficking.
In Raji B cells, which exhibit constitutive NF-??B activation driven by EBV oncoproteins, COMMD2 knockout heightens NF-??B responses, offering a model to study the contribution of this pathway to lymphomagenesis. The disruption also impacts endosomal sorting and copper balance, processes increasingly recognized in lymphocyte proliferation and survival. This polyclonal population captures a range of editing efficiencies, reflecting the heterogeneity typical of tumor environments and facilitating robust comparative analyses.
Researchers can employ this model for luciferase-based NF-??B reporter assays, western blot analysis of p65 and I??B??, and co-immunoprecipitation of COMMD2 with CCC components. Transcriptional profiling of NF-??B targets (e.g., IL-6, A20) by RT-qPCR, copper uptake assays, and flow cytometric assessment of apoptosis (Annexin V) and proliferation (MTT) further extend its utility. These polyclonal knockout cells are ideal for screening anti-inflammatory compounds, dissecting B-cell lymphoma biology, and exploring copper metabolism. For technical support or custom solutions, contact Ascent Research.