B2M Knockout LoVo Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the LoVo human colorectal adenocarcinoma epithelial cell line. The product features CRISPR/Cas9-mediated disruption of the B2M gene, encoding beta-2-microglobulin, an essential subunit of major histocompatibility complex (MHC) class I molecules. This polyclonal knockout pool contains a heterogeneous mixture of B2M-null cells, enabling pooled functional studies without clonal selection.
The LoVo cell line was established from a metastatic supraclavicular lymph node of a 56-year-old male with colorectal adenocarcinoma. As an epithelial cell model of metastatic colorectal cancer, LoVo cells are widely used in studies of tumor biology, invasion, and therapeutic response. Their genetic background retains key features of colorectal adenocarcinoma and provides a relevant system for investigating cancer immune interactions.
B2M encodes beta-2-microglobulin, which non-covalently associates with MHC class I heavy chains (HLA-A, HLA-B, HLA-C) to form functional peptide-presenting complexes. This assembly is facilitated by the peptide loading complex, including tapasin, calreticulin, and ERp57. B2M expression is transcriptionally regulated by interferon-gamma (IFN-??) via IRF1 and NF-??B, linking it to pro-inflammatory cytokine signaling. On the cell surface, MHC class I?CB2M complexes present endogenous antigenic peptides processed by the proteasome and transported by TAP1/TAP2. These complexes engage CD8+ T cell receptors, triggering cytotoxic T lymphocyte responses. Additionally, natural killer (NK) cell receptors such as KIRs and LILRB1 monitor MHC class I expression; B2M loss disrupts this balance, potentially increasing NK cell?Cmediated recognition.
In the LoVo colorectal cancer context, B2M knockout eliminates MHC class I surface expression, severely impairing presentation of tumor-associated antigens to CD8+ T cells. This mimics a common immune evasion mechanism observed in colorectal carcinoma and other malignancies, where B2M mutations or downregulation correlates with poor prognosis and resistance to checkpoint blockade. Consequently, the B2M Knockout LoVo model provides a physiologically relevant platform to dissect mechanisms of primary and acquired immune escape. Notably, the loss of MHC class I renders cells susceptible to NK cell cytotoxicity due to missing-self recognition, highlighting the dual role of B2M in adaptive and innate immune surveillance. This model thus enables investigations into the interplay between MHC class I loss, CD8+ T cell evasion, and NK cell activation in a colorectal cancer background.
Researchers can utilize B2M Knockout LoVo Polyclonal Cells in a wide array of immuno-oncology applications. The cells are suitable for co-culture assays with antigen-specific CD8+ T cells to study impaired cytotoxicity and for NK cell killing assays to assess enhanced susceptibility. They can be employed in xenograft tumor growth studies to evaluate in vivo immune escape dynamics and in drug sensitivity screens to explore synthetic lethality or therapeutic vulnerabilities. Flow cytometry and western blotting can confirm MHC class I loss and B2M ablation, while transcriptomic profiling by RNA-seq allows global analysis of altered gene expression. Additionally, this model supports investigation of the interferon-gamma signaling axis and its downstream effects in the absence of MHC class I antigen presentation. For further information, please contact Ascent Research.
