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 CD1 and Qa.
An additional function is association 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 increased iron uptake from food and decreased iron release from recycled red blood cells in the MPS (mononuclear phagocyte system) respectively. Loss of this function causes iron excess and hemochromatosis.
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.
Levels of β2 microglobulin can be elevated in multiple myeloma and lymphoma, though in these cases primary amyloidosis (amyloid light chain) and secondary amyloidosis (amyloid associated protein) are more common.[clarification needed] The normal value of β2 microglobulin is <2 mg/L. However, with respect to multiple myeloma, the levels of β2 microglobulin may also be at the other end of the spectrum.[clarification needed] Diagnostic testing for multiple myeloma includes obtaining the β2 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 >4mg/L has a median survival of only 12 months. β2 microglobulin levels cannot, however, distinguish between monoclonal gammopathy of uncertain significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.
^Pignone M, Nicoll D; McPhee SJ (2004). Pocket guide to diagnostic tests (4th ed.). New York: McGraw-Hill. p. 191. ISBN0-07-141184-4.
^Munshi NC, Longo DL, Anderson KC (2011). "Chapter 111: Plasma Cell Disorders". In Loscalzo J, Longo DL, Fauci AS, Dennis LK, Hauser SL. Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill Professional. pp. 936–44. ISBN0-07-174889-X.
Huang WC, Wu D, Xie Z, Zhau HE, Nomura T, Zayzafoon M, Pohl J, Hsieh CL, Weitzmann MN, Farach-Carson MC, Chung LW (2006). "Beta2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis". Cancer Res. 66 (18): 9108–16. doi:10.1158/0008-5472.CAN-06-1996. PMID16982753.
Okon M, Bray P, Vucelić D (1992). "1H NMR assignments and secondary structure of human beta 2-microglobulin in solution". Biochemistry. 31 (37): 8906–15. doi:10.1021/bi00152a030. PMID1390678.
Guo HC, Jardetzky TS, Garrett TP, et al. (1992). "Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle". Nature. 360 (6402): 364–6. doi:10.1038/360364a0. PMID1448153.
Gattoni-Celli S, Kirsch K, Timpane R, Isselbacher KJ (1992). "Beta 2-microglobulin gene is mutated in a human colon cancer cell line (HCT) deficient in the expression of HLA class I antigens on the cell surface". Cancer Res. 52 (5): 1201–4. PMID1737380.
Caruana RJ, Lobel SA, Leffell MS, et al. (1991). "Tumor necrosis factor, interleukin-1 and beta 2-microglobulin levels in chronic hemodialysis patients". The International journal of artificial organs. 13 (12): 794–8. PMID2289831.
Connors LH, Shirahama T, Skinner M, et al. (1985). "In vitro formation of amyloid fibrils from intact beta 2-microglobulin". Biochem. Biophys. Res. Commun. 131 (3): 1063–8. doi:10.1016/0006-291X(85)90198-6. PMID2413854.
Hochman JH, Shimizu Y, DeMars R, Edidin M (1988). "Specific associations of fluorescent beta-2-microglobulin with cell surfaces. The affinity of different H-2 and HLA antigens for beta-2-microglobulin". J. Immunol. 140 (7): 2322–9. PMID2450918.
Homma N, Gejyo F, Isemura M, Arakawa M (1989). "Collagen-binding affinity of beta-2-microglobulin, a preprotein of hemodialysis-associated amyloidosis". Nephron. 53 (1): 37–40. doi:10.1159/000185699. PMID2674742.
Hönig R, Marsen T, Schad S, et al. (1989). "Correlation of beta-2-microglobulin concentration changes to changes of distribution volume". The International journal of artificial organs. 11 (6): 459–64. PMID3060434.
Bjorkman PJ, Saper MA, Samraoui B, et al. (1987). "Structure of the human class I histocompatibility antigen, HLA-A2". Nature. 329 (6139): 506–12. doi:10.1038/329506a0. PMID3309677.
Güssow D, Rein R, Ginjaar I, et al. (1987). "The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit". J. Immunol. 139 (9): 3132–8. PMID3312414.
Cunningham BA, Wang JL, Berggård I, Peterson PA (1974). "The complete amino acid sequence of beta 2-microglobulin". Biochemistry. 12 (24): 4811–22. doi:10.1021/bi00748a001. PMID4586824.
Matoba R, Okubo K, Hori N, et al. (1994). "The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression". Gene. 146 (2): 199–207. doi:10.1016/0378-1119(94)90293-3. PMID8076819.