The B2M Knockout UM-UC-3 Polyclonal Cells product consists of a polyclonal population of UM-UC-3 human urinary bladder carcinoma cells that have been subjected to CRISPR/Cas9-mediated disruption of the B2M gene. This polyclonal knockout pool provides a heterogeneous collection of edited cells, enabling researchers to investigate loss-of-function phenotypes of beta-2-microglobulin without the constraints of single-cell clonal selection. The product serves as a versatile tool for studying the consequences of B2M ablation in an epithelial cancer background.
The UM-UC-3 cell line is derived from a grade III transitional cell carcinoma of the urinary bladder in a male patient, representing a widely used model for high-grade bladder cancer. These adherent epithelial cells exhibit characteristics of advanced transitional cell carcinoma, including invasive potential and aberrant growth signaling. As a primary tumor-derived line, UM-UC-3 retains key features of the original malignancy, making it suitable for xenograft and in vitro functional studies. The host cell??s epithelial origin and tumorigenic properties provide a relevant context for examining the role of B2M in tumor immunology.
B2M encodes beta-2-microglobulin, a soluble protein that non-covalently associates with MHC class I heavy chains (HLA-A, HLA-B, HLA-C) to form functional peptide-presenting complexes on the cell surface. This heterodimerization is essential for the stable expression of MHC class I molecules and their loading with antigenic peptides via the peptide-loading complex, which includes TAP1/TAP2, tapasin, calreticulin, and ERp57. B2M expression is transcriptionally regulated by interferons (IFNG, IFNA, IFNB) through JAK-STAT signaling, involving STAT1, IRF1, and NF-kB1. Beyond adaptive immunity, B2M interacts with CD1D for lipid antigen presentation and with HFE and TFRC to modulate iron homeostasis, linking it to broader physiological processes.
Disruption of B2M in UM-UC-3 cells leads to loss of surface MHC class I expression, mimicking a common immune evasion strategy observed in bladder carcinomas and other malignancies. Consequently, these knockout cells are rendered resistant to CD8+ cytotoxic T lymphocyte-mediated recognition while potentially enhancing susceptibility to NK cell killing due to missing-self responses. This model enables dissection of the dual roles of B2M in adaptive and innate immunity within the tumor microenvironment. Moreover, it facilitates investigation of the interplay between interferon signaling and antigen presentation pathways, and the consequences of impaired MHC class I on tumor progression and metastasis.
Typical applications of this product include flow cytometry-based quantification of MHC class I surface loss, western blotting and RT-qPCR confirmation of B2M ablation, and functional assays such as CD8+ T cell cytotoxicity and NK cell degranulation tests. Researchers may employ these cells in co-culture systems to evaluate tumor immune escape mechanisms, in peptide-binding studies to assess antigen presentation machinery, or in xenograft models to study allograft rejection and tumor growth. The polyclonal nature of the knockout population provides a realistic spectrum of editing outcomes, suitable for high-throughput screening and pooled phenotypic analyses. For more information or to inquire about this product, please contact Ascent Research.
