MAP3K8 Knockout Raji Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population derived from the Raji B lymphoblast cell line, engineered to disrupt the MAP3K8 gene and eliminate functional expression of the TPL2 serine/threonine kinase. This polyclonal pool provides a heterogeneous loss-of-function model for studying TPL2-dependent signaling without the constraints of single-cell clonal selection, enabling robust interrogation of pathway biology in a B-lymphocyte context.
The Raji cell line is a widely used human B lymphoblast model originating from a Burkitt lymphoma patient. These Epstein-Barr virus (EBV)-positive cells mimic key characteristics of activated B lymphocytes, including surface immunoglobulin expression, antigen presentation capacity, and the ability to secrete cytokines. Their transformed phenotype and intact inflammatory signaling pathways make them an ideal host for dissecting the molecular regulation of immune responses.
MAP3K8 (TPL2) functions as a critical downstream mediator of pro-inflammatory receptors, including Toll-like receptors (TLRs), the IL-1 receptor, and tumor necrosis factor receptor (TNFR). In unstimulated cells, TPL2 is sequestered in an inactive complex with NFKB1 p105 and the adaptor protein ABIN-2 (TNIP2). Upon receptor engagement by ligands such as LPS, IL-1beta, or CD40L, the IKK complex phosphorylates p105, triggering its degradation and releasing active TPL2. Free TPL2 subsequently phosphorylates and activates MEK1 (MAP2K1) and MEK2 (MAP2K2), which in turn phosphorylate ERK1 (MAPK3) and ERK2 (MAPK1). Activated ERK1/2 translocates to the nucleus, stimulating AP-1 transcription factors (c-Fos/c-Jun) and promoting the expression of pro-inflammatory mediators including TNF-alpha, IL-6, and COX-2.
In the Raji B-cell context, MAP3K8 knockout disrupts a central axis of inflammatory signal transduction. Raji cells express functional TLRs, CD40, and TNFR superfamily members, allowing direct assessment of how loss of TPL2 alters cytokine production, cell activation, and proliferation. This model is particularly relevant to studies of B-cell lymphomas, where aberrant MAPK/ERK and NF-kappaB signaling contribute to pathogenesis, as well as to autoimmune conditions such as rheumatoid arthritis and inflammatory bowel disease, where TPL2 drives pathogenic cytokine secretion. The polyclonal nature of the knockout population minimizes concerns about clonal drift and artifact, providing a more physiological representation of gene disruption in a bulk culture.
Researchers can employ MAP3K8 Knockout Raji Polyclonal Cells in a broad range of assays: western blotting for phospho-ERK to quantify MAPK pathway activity; ELISA or RT-qPCR for TNF-alpha, IL-6, and other TPL2-dependent cytokines; flow cytometric detection of B cell activation markers CD69 and CD86; co-immunoprecipitation to examine TPL2-p105 complex formation; and cell proliferation assays to evaluate TPL2 inhibitor candidates. These cells serve as a platform for mechanistic dissection of kinase signaling, high-throughput compound screening, and validation of therapeutic targets in inflammatory diseases and lymphoma. For additional product information or technical support, please contact Ascent Research.
