“Beta-2 microglobulin”的意思、由来-开放百科全书

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 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.{{citation needed|date=August 2016}}

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.){{citation needed|date=August 2016}}

Clinical significance

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

Low levels of β₂ microglobulin can indicate non-progression of HIV.{{citation needed|date=April 2016}}

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.{{clarify|date=April 2016}} The normal value of β₂ microglobulin is <2 mg/L.^[5] However, with respect to multiple myeloma, the levels of β₂ microglobulin may also be at the other end of the spectrum.{{clarify|date=April 2016}} Diagnostic testing for multiple myeloma includes obtaining the β₂ microglobulin level, for this level is an important prognostic indicator. {{as of|2011}} 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.^[6] β₂ microglobulin levels cannot, however, distinguish between monoclonal gammopathy of undetermined significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.^[7]^[8]

Loss-of-function mutations in this gene have been reported in cancer patients unresponsive to immunotherapies.{{citation needed|date=August 2017}}

References

1. ^{{cite web | title = Entrez Gene: Beta-2-microglobulin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=567| accessdate = }}
2. ^¹{{cite journal | vauthors = Güssow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, Ploegh HL | title = The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit | journal = J. Immunol. | volume = 139 | issue = 9 | pages = 3132–8 | date=1 November 1987| pmid = 3312414 | url = http://www.jimmunol.org/cgi/content/abstract/139/9/3132 }}
3. ^{{cite journal | vauthors = Cunningham BA, Wang JL, Berggård I, Peterson PA | title = The complete amino acid sequence of beta 2-microglobulin | journal = Biochemistry | volume = 12 | issue = 24 | pages = 4811–22 |date=November 1973 | pmid = 4586824 | doi = 10.1021/bi00748a001| url = }}
4. ^{{cite journal | vauthors = Suggs SV, Wallace RB, Hirose T, Kawashima EH, Itakura K | title = Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 78 | issue = 11 | pages = 6613–7 |date=November 1981 | pmid = 6171820 | pmc = 349099 | doi = 10.1073/pnas.78.11.6613| url = }}
5. ^{{cite book | author = Pignone M, Nicoll D | author2 = McPhee SJ | title = Pocket guide to diagnostic tests | edition = 4th | publisher = McGraw-Hill | location = New York | year = 2004 | pages =191 | isbn = 0-07-141184-4 }}
6. ^{{cite book | veditors = Loscalzo J, Longo DL, Fauci AS, Dennis LK, Hauser SL | title = Harrison's Principles of Internal Medicine | vauthors = Munshi NC, Longo DL, Anderson KC | chapter = Chapter 111: Plasma Cell Disorders | pages = 936–44| edition = 18th | publisher = McGraw-Hill Professional | location = | year = 2011 | isbn = 0-07-174889-X }}
7. ^Rajkumar S. V. "MGUS and Smoldering Multiple Myeloma: Update on Pathogenesis, Natural History, and Management." Hematology, American Society of Hematology Education Program. doi: 10.1182/asheducation-2005.1.340 (ASH Education Book January 1, 2005 vol. 2005 no. 1 340-345) Accessed 23 May 2014.
8. ^Bataille R. and Klein B. "Serum levels of beta-2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of uncertain significance." Blood 1992 80(9) p2433 Accessed 23 May 2014.

Structure and function

Clinical significance

References

Further reading

External links