Beta-2 microglobulin

β2 microglobulin also known as B2M is a component of is_associated_with::MHC class I molecules, which are present on all nucleated cells (excludes is_associated_with::red blood cells). In humans, the β2 microglobulin is_associated_with::protein is encoded by the B2M is_associated_with::gene.

Structure and function
β2 microglobulin lies beside the α3 chain on the cell surface. Unlike α3, β2 has no transmembrane region. Directly above β2 (that is, further away from the cell) lies the α1 chain, which itself is next to the α2.

β2 microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as is_associated_with::CD1 and Qa.

An additional function is association with the is_associated_with::HFE protein, together regulating the expression of is_associated_with::hepcidin in the is_associated_with::liver which targets the iron transporter is_associated_with::ferroportin on the cytoplasmic membrane of is_associated_with::enterocytes and is_associated_with::macrophages for degradation resulting in decreased iron uptake from food and iron release from recycled red blood cells respectively. Loss of this function causes iron excess and is_associated_with::hemochromatosis.

Clinical significance
In patients on long-term is_associated_with::hemodialysis, it can aggregate into is_associated_with::amyloid fibers that deposit in joint spaces, a disease known as is_associated_with::dialysis-related amyloidosis.

Mice models deficient for the β2 microglobulin gene have been engineered. These mice demonstrate that β2 microglobulin is necessary for cell surface expression of MHC class I and stability of the peptide binding groove. In fact, in the absence of β2 microglobulin, very limited amounts of MHC class I (classical and non-classical) molecules can be detected on the surface. In the absence of MHC class I, is_associated_with::CD8 T cells cannot develop. (CD8 T cells are a subset of T cells involved in the development of acquired immunity.) Low levels of β2 microglobulin can indicate non-progression of HIV.

Levels of beta-2 microglobulin can be elevated in is_associated_with::multiple myeloma and is_associated_with::lymphoma, though in these cases primary amyloidosis (amyloid light chain) and secondary amyloidosis (amyloid associated protein) are more common. The normal value of beta-2 microglobulin is <2 mg/L. However, with respect to multiple myeloma, the levels of beta2-microglobulin may also be at the other end of the spectrum. Diagnostic testing for multiple myeloma includes obtaining the beta2-microglobulin level, for this level is an important prognostic indicator. A patient with a level <4 mg/L is expected to have a median survival of 43 months, while one with a level >4 mg/L has a median survival of only 12 months. Beta-2 microglobulin levels cannot, however, distinguish between is_associated_with::monoclonal gammopathy of uncertain significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.