The B2m Knockout Hepa 1-6 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Hepa 1-6 mouse hepatoma cell line. This population carries targeted disruption of the endogenous B2m gene, resulting in a loss-of-function model for beta-2-microglobulin. The polyclonal format provides a diverse mixture of edited cells, representing a range of gene disruption events, and is suitable for pooled functional studies without clonal selection.
Hepa 1-6 is a well-established mouse hepatocellular carcinoma epithelial cell line, originally derived from the BW7756 tumor and syngeneic to C57L mice. It is widely used as a model for hepatoma biology, hepatic function, and liver cancer research. These cells retain hepatic characteristics and form tumors in syngeneic hosts, enabling in vivo and in vitro immuno-oncology studies.
The B2m gene encodes beta-2-microglobulin, an essential subunit of major histocompatibility complex (MHC) class I molecules. It is required for the stable cell surface expression of MHC class I and the presentation of endogenous peptides to CD8+ T cells. B2m expression is transcriptionally regulated by IFN-gamma and type I interferons through pathways involving NLRC5, IRF1, and NF-??B. Within the endoplasmic reticulum, beta-2-microglobulin associates with MHC class I heavy chains (such as H2-K1 and H2-D1), tapasin, the transporter associated with antigen processing (TAP1/TAP2), calnexin, calreticulin, and ERp57 (Pdia3) to form the peptide-loading complex. Loss of B2m therefore disrupts this complex, abolishing peptide loading and surface MHC class I expression, which in turn impairs CD8+ T cell priming and alters natural killer (NK) cell recognition via Ly49 receptors.
In the Hepa 1-6 hepatocellular carcinoma context, disruption of B2m leads to complete loss of surface MHC class I molecules, mimicking a common immune evasion mechanism observed in many cancers. This defect cripples antigen presentation, enabling tumor cells to escape cytotoxic T lymphocyte-mediated killing. Simultaneously, the absence of MHC class I relieves inhibitory signaling through NK cell Ly49 receptors, potentially enhancing NK cell susceptibility under certain conditions. This dual modulation of adaptive and innate immunity makes the knockout model a powerful tool for dissecting tumor?Chost immune interactions.
The B2m Knockout Hepa 1-6 Polyclonal Cells are ideally suited for tumor immunology research, including studies on immune evasion, CD8+ T cell responses, and NK cell function. They enable syngeneic mouse tumor models to evaluate the role of MHC class I in therapeutic resistance and to validate immunotherapy targets. Typical assays include flow cytometric assessment of MHC class I surface deficiency, co-culture T cell killing assays, NK cell cytotoxicity tests, RNA sequencing for transcriptomic profiling, western blotting for pathway analysis, and IFN-gamma treatment response experiments to probe inducible gene expression. For additional information, please contact Ascent Research.
