B2Mmutationer

B2Mmutationer is a term referring to genetic alterations in the B2M gene, which encodes beta-2-microglobulin, a non-polypeptide component essential for the stability and cell-surface expression of MHC class I molecules. The B2M gene is foundational for antigen presentation to CD8+ T cells, and mutations can be inherited (germline) or acquired in somatic cells.

Mutations in B2M can take several forms, including frameshift, nonsense, splice-site, and missense changes. When B2M is defective, the heavy chains of MHC class I molecules often fail to assemble properly, leading to reduced or absent MHC class I on the cell surface. This disrupts normal antigen presentation and can alter interactions with cytotoxic T cells and natural killer cells. In tumors, somatic B2M mutations are a recognized mechanism of immune escape, allowing cancer cells to evade T cell–mediated surveillance.

Clinically, germline B2M defects can cause MHC class I deficiency, resulting in increased susceptibility to viral infections and immunodeficiency. In cancer, B2M mutations have been observed across multiple tumor types, including melanomas, colorectal cancers, and bladder cancers, and are frequently associated with impaired responses to therapies that rely on MHC class I–restricted antigen presentation. They can influence prognosis and inform therapeutic decision-making.

Diagnosis typically involves sequencing approaches such as targeted gene panels or whole-exome sequencing to identify B2M alterations, complemented by immunohistochemistry or flow cytometry to assess MHC class I expression on cells. Therapeutic considerations include potential reduced efficacy of PD-1/PD-L1 inhibitors in tumors harboring B2M mutations, with research exploring alternative strategies that do not depend on intact MHC class I–mediated antigen presentation.