Beta-2 microglobulin (B2M), a 12 kDa protein, is a non-polymorphic component of the major histocompatibility complex (MHC) class I molecules, essential for antigen presentation to cytotoxic T cells. It forms the light chain of MHC-I, stabilizing its structure and enabling immune recognition of pathogens or abnormal cells. Beyond its immunological role, B2M is constitutively expressed on nucleated cells and freely circulates in bodily fluids, with serum levels influenced by glomerular filtration. Elevated B2M levels are clinically linked to renal dysfunction, inflammatory disorders, and malignancies like multiple myeloma, where it serves as a prognostic biomarker.
In cancer biology, B2M loss or mutations are associated with immune evasion, as impaired MHC-I expression allows tumor cells to escape T-cell surveillance. This has spurred interest in B2M-targeting antibodies for immunotherapy. Anti-B2M antibodies are being explored to modulate immune responses—either by blocking MHC-I to suppress autoimmune reactions or by enhancing antigen presentation in tumors. Additionally, B2M-targeting CAR-T cells and antibody-drug conjugates (ADCs) are under investigation for hematologic cancers.
In neurodegenerative diseases, B2M aggregates contribute to dialysis-related amyloidosis, driving research into antibodies that clear pathologic B2M deposits. Despite promise, challenges like on-target/off-tumor toxicity and resistance mechanisms require further optimization. Overall, B2M antibodies represent a versatile tool bridging diagnostics, immune modulation, and targeted therapies.