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Beta-2-microglobulin (B2M) is an invariant subunit required for the assembly of human leukocyte antigen complex (HLA-I), which is present on the plasma membrane of most nucleated cells and participates in endogenous expression of an antigenic peptides that is self-degrading or non-self-degrading.
B2M, a light chain subunit of the major histocompatibility complex (MHC) class I complex, is associated with the heavy chain (α-chain) of the complex on the surface of nearly all nucleated cells. It exists in both membrane and soluble B2M, which can be exchanged freely.
Fig 1. Bipartite B2M interaction networks (Engin et al. PLoS One. 2016).
Unlike most cancer genes known to us, B2M is predominantly located on partner genes that affect tumor suppressor genes. Most of those partners compete with each other to bind the same site on B2M.
Aberrant B2M Protein Expression in Diffuse Large B-cell Lymphoma (DLBCL)
Diffuse large B-cell lymphoma (DLBCL) is the most common form of adult non-Hodgkin's lymphoma (NHL), accounting for 30-40%. It was reported that B2M gene lesions are associated with defective HLA-I in a small number of lymphomas originating from the testis or the central nervous system. B2M mutations are present in both the GCB and ABC/non-classified DLBCL subtype, but not in other mature B-NHL. These results suggest that B2M plays a specific role in the pathogenesis of DLBCL. The DLBCL biopsies are analyzed by using HC-10 antibody to investigate whether B2M gene alteration caused a disorder of cell surface HLA-1 expression. The results indicate that direct inactivation of the B2M gene by deletion and/or mutation occurs in a sizable fraction of DLBCLs. Inactivation of B2M is a recurrent event in DLBCLs of both the GCB- and ABC-type, suggesting a pathogenesis in this disease.
Human Epithelial-type Ovarian Tumour Marker beta-2-microglobulin is regulated by the TGF-β Signaling Pathway
The functional study of B2M in cancer cells has shown that B2M plays an important role in promoting cancer cell growth. The growth-stimulatory activity of B2M may be associated with the antagonistic activity of B2M to the transforming growth factor-β (TGF-β)-induced growth inhibition. TGF-β belongs to a superfamily of secreted cytokines and plays a pivotal role in immunosuppression.
It was found that the expression of B2M in ovarian borderline and malignant tumors is higher than that of benign tumors and normal controls, but not related to age, tumor size, lymph node metastasis and clinical stage. Knockout of B2M results in a decrease in OC cell proliferation, migration and invasion. The expression of B2M is down-regulated by TGF-β1 in OC cells, which is abolished in the presence of the inhibitor of TGF-β type I receptor.