Beta-2 microglobulin (b2m) is a naturally occurring protein in the human body. It is one of two polypeptide chains that make up the structure of a major histocompatibility complex (MHC) Class I molecule. Certain characteristics of b2m make it suitable for detecting tumor cells, especially in blood and kidney cells. B2m also has been used to evaluate kidney function following a kidney transplant operation, and as a prognostic tool for immune system-related diseases.
This large protein belongs to a class of histocompatibility molecules, which are glycoproteins expressed at the surface of nucleated white blood cells in vertebrates. MHC Class I molecules such as b2m are useful for detecting incompatible or genetically different cells within the body. Some key characteristics of beta-2 microglobulin are that it has no transmembrane region, associates with the alpha chain of MHC Class I molecules by non-covalent bonds and associates with the human hemochromatosis (HFE) protein. Normal levels of beta-2 microglobulin range from 1 to 2.1 micrograms per milliliter (µg/mL); upper normal range values are 2.0 to 2.5 µg/mL.
An MHC Class I molecule consists of two polypeptide chains, a long alpha chain on the left and a shorter chain on the right that is beta-2 microglobulin. Histocompatibility molecules also are referred to as antigens because of their ability to elicit an immune system response. Basically, for a tissue transplant to be successful, the MHC of the tissue’s cells must be compatible between the donor and the recipient. Additionally, if an unhealthy cell containing foreign material from a disease, virus or bacteria is detected, then the MHC Class I molecules will flag them as a signal for the immune system to attack the cells containing foreign proteins. In clinical studies, the level of beta-2 microglobulin production is directly associated with lymphocyte activation, a signature immune system response.
B2m molecules have been targeted in cancer treatment and immune system disorders in which T-cells are involved. Clinical studies with b2m-deficient mice have demonstrated an important role of beta-2 microglobulin in cellular surface expression of MHC Class I molecules and peptide binding. Without peptide binding and subsequent protein synthesis, the production of certain immune system-related cells, including T-cells, is halted when b2m is absent. Immunology assays have been developed using b2m as a tumor marker.
A physician or oncologist may perform a b2m test to get a general idea of how much cancer may be present in a patient. Elevated b2m levels can indicate multiple myeloma, lymphoma or leukemia. Both blood and urine tests for beta-2 microglobulin have been used for patients with kidney disease following a kidney transplant. B2m can distinguish between glomular and tubular kidney disorders. In rare cases, b2m tests are used to evaluate the effects of a disease on the central nervous system.