DEFINITION
β2 microglobulin (B2M) is a small protein that occurs as a monomer in relatively low concentration in biological fluids (1,8 mg/L). It is a component of MHC class I molecules, which are present on all nucleated cells, and that are involved in self-recognition and in defense against micro-organisms.
GENE
In humans, the β2 microglobulin protein is encoded by the B2M gene.
STRUCTURE and IMAGES
Gene Expression
There is an elevated expression of B2M gene in white blood cells, because of the higher exposition of MHC Class 1 molecules in this cell population.
Moreover the increased expression in colon and small intestine cells is probably related to the function of iron absorption of these organs.
Protein Aminoacids Percentage
FUNCTION
Beta-2 microglobulin is involved in the composition of MHC class 1 molecules. It associates with 3 alpha-chains, stabilizing the binding groove. This structure allows all nucleated cells to expose self-antigens out of the cytoplasmic membrane, enabling the immune system of the individual to recognize the cell as 'self'.
Beta-2 microglobulin is also associated with the HFE protein, together regulating the expression of hepcidin in the liver which targets the iron transporter ferroportin on the cytoplasmic membrane of enterocytes and macrophages for degradation resulting in decreased iron uptake from food and iron release from recycled red blood cells respectively.
CLINICAL SIGNIFICANCE
Serum beta2 microglobulin is an easy parameter to measure and it is over-expressed in a large number of lymphoproliferative diseases,like multiple myeloma and lymphoma (i.e. post-transplant lymphoproliferative disease and extranodal natural killer/T cell lymphoma), thus it is used as a prognostic factor.
In patients that undergo long-term hemodialisys, like patients suffering from chronic renal failure, B2M protein can lead to haemodialysis-associated amyloidosis: the protein is unable to cross the dialysis filter so it gradually accumulates in the blood leading to 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, 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.
Beta-2 microglobulin is also involved in iron blood levels control: it associates with HFE protein, that regulates the trascription of hepcidin, a protein syntetized in the liver who targets ferroportin, an iron transporter on the cytoplasmatic membrane of enterorocytes and macrophages. In fact, a loss of B2m in murin models causes also hemochromathosis.
B2M is also expressed in the CNS (SNC), especially in the spinal cord, and it has been recently associated to the ALS (SLA), a neurodegenerative disease that causes rapidly progressive weakness and muscle atrophy.
Carl Margaria e Michele Ravotti
