View source for Beta-2 microglobulin

{{short description|Component of MHC class I molecules}}
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{{Infobox_gene}}
'''β<sub>2</sub> microglobulin''' ('''B2M''') is a component of [[MHC class I]] molecules. MHC class I molecules have α<sub>1</sub>, α<sub>2</sub>, and α<sub>3</sub> proteins which are present on all nucleated cells (excluding [[red blood cell]]s).<ref name="entrez_567">{{cite web | title = Entrez Gene: Beta-2-microglobulin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=567}}</ref><ref name="pmid3312414">{{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 = Journal of Immunology | volume = 139 | issue = 9 | pages = 3132–3138 | date = November 1987 | pmid = 3312414 | doi = 10.4049/jimmunol.139.9.3132 | s2cid = 38290153 | doi-access = free }}</ref>  In humans, the β<sub>2</sub> microglobulin [[protein]]<ref name="pmid4586824">{{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 = 4811–4822 | date = November 1973 | pmid = 4586824 | doi = 10.1021/bi00748a001 }}</ref> is encoded by the ''B2M'' [[gene]].<ref name="pmid3312414"/><ref name="pmid6171820">{{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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 11 | pages = 6613–6617 | date = November 1981 | pmid = 6171820 | pmc = 349099 | doi = 10.1073/pnas.78.11.6613 | doi-access = free | bibcode = 1981PNAS...78.6613S }}</ref>

==Structure and function==
[[Image:MHC Class 1.svg|thumb|left|Schematic representation of MHC class I]]
β<sub>2</sub> microglobulin lies beside the α<sub>3</sub> chain on the cell surface. Unlike α<sub>3</sub>, β<sub>2</sub> has no [[Transmembrane protein|transmembrane]] region. Directly above β<sub>2</sub> (that is, further away from the cell) lies the α<sub>1</sub> chain, which itself is next to the α<sub>2</sub>.

β<sub>2</sub> microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as [[CD1]] (5 genes in humans), [[Major histocompatibility complex, class I-related|MR1]], the [[neonatal Fc receptor]] (FcRn), and Qa-1 (a form of [[alloantigen]]). Nevertheless, the β<sub>2</sub> microglobulin gene is outside of the MHC (HLA) locus, on a different chromosome.

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 basolateral membrane of [[enterocytes]] and cell membrane of [[macrophages]] for degradation resulting in decreased 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]].<ref>{{cite book | vauthors = Hundall SD | title = Hematology: A Pathophysiologic Approach | edition = 1st | date = 2011 | chapter = Chapter 3: Iron, Heme, and Hemoglobin | pages = 17–25 | publisher = Elsevier - Health Sciences Division | isbn = 978-0-323-04311-3 }}</ref>

In a [[cytomegalovirus]] infection, a viral protein binds to β<sub>2</sub> microglobulin, preventing assembly of MHC class I molecules and their transport to the plasma membrane.{{citation needed|date=June 2024}}

Mice models deficient for the β<sub>2</sub> microglobulin gene have been engineered. These mice demonstrate that β<sub>2</sub> microglobulin is necessary for cell surface expression of MHC class I and stability of the peptide-binding groove. In fact, in the absence of β<sub>2</sub> microglobulin, very limited amounts of MHC class I (classical and non-classical) molecules can be detected on the surface ([[bare lymphocyte syndrome]] or BLS). In the absence of MHC class I, [[CD8]]<sup>+</sup> T cells cannot develop. (CD8<sup>+</sup> 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 β<sub>2</sub> microglobulin can indicate non-progression of HIV.<ref>{{cite journal | vauthors = Rao M, Sayal SK, Uppal SS, Gupta RM, Ohri VC, Banerjee S | title = Beta-2-Microglobulin Levels in Human-Immunodeficiency Virus Infected Subjects | journal = Medical Journal, Armed Forces India | volume = 53 | issue = 4 | pages = 251–254 | date = October 1997 | pmid = 28769505 | pmc = 5531080 | doi = 10.1016/S0377-1237(17)30746-3 }}</ref>

Levels of  β<sub>2</sub> 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  β<sub>2</sub> microglobulin is < 2&nbsp;mg/L.<ref name="isbn0-07-141184-4">{{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 = [https://archive.org/details/isbn_9780071411844/page/191 191] | isbn = 0-07-141184-4 | url = https://archive.org/details/isbn_9780071411844/page/191 }}</ref> However, with respect to multiple myeloma, the levels of β<sub>2</sub> microglobulin may also be at the other end of the spectrum.<ref>{{cite web |url= https://www.lecturio.com/concepts/amyloidosis/ | title= Amyloidosis | website= The Lecturio Medical Concept Library |access-date= 28 June 2021}}</ref>  Diagnostic testing for multiple myeloma includes obtaining the  β<sub>2</sub> microglobulin level, for this level is an important prognostic indicator.  {{as of|2011}}, a patient with a level < 4&nbsp;mg/L is expected to have a median survival of 43 months, while one with a level > 4&nbsp;mg/L has a median survival of only 12 months.<ref name="isbn0-07-174889-X">{{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 | year = 2011 | isbn = 978-0-07-174889-6 }}</ref>  β<sub>2</sub> microglobulin levels cannot, however, distinguish between [[monoclonal gammopathy of undetermined significance]] (MGUS), which has a better prognosis, and ''smouldering'' (low grade) myeloma.<ref>{{cite journal | vauthors = Rajkumar SV | title = MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management | journal = Hematology. American Society of Hematology. Education Program | volume = 2005 | pages = 340–345 | year = 2005 | pmid = 16304401 | doi = 10.1182/asheducation-2005.1.340 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bataille R, Klein B | title = Serum levels of beta 2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of undetermined significance | journal = Blood | volume = 80 | issue = 9 | pages = 2433–2434 | date = November 1992 | pmid = 1421418 | doi = 10.1182/blood.V80.9.2433.2433 | doi-access = free }}</ref>

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

==Virus relevance==
β<sub>2</sub> microglobulin has been shown to be of high relevance for viral entry of Coxsackievirus A9 and Vaccinia virus (a Poxvirus).<ref>{{cite journal | vauthors = Matía A, Lorenzo MM, Romero-Estremera YC, Sánchez-Puig JM, Zaballos A, Blasco R | title = Identification of β2 microglobulin, the product of B2M gene, as a Host Factor for Vaccinia Virus Infection by Genome-Wide CRISPR genetic screens | journal = PLOS Pathogens | volume = 18 | issue = 12 | pages = e1010800 | date = December 2022 | pmid = 36574441 | pmc = 9829182 | doi = 10.1371/journal.ppat.1010800 | doi-access = free }}</ref> For Coxsackievirus A9, it is likely that β<sub>2</sub> microglobulin is required for the transport to plasma membrane of the identified receptor, the Human Neonatal Fc Receptor (FcRn).<ref>{{cite journal | vauthors = Zhao X, Zhang G, Liu S, Chen X, Peng R, Dai L, Qu X, Li S, Song H, Gao Z, Yuan P, Liu Z, Li C, Shang Z, Li Y, Zhang M, Qi J, Wang H, Du N, Wu Y, Bi Y, Gao S, Shi Y, Yan J, Zhang Y, Xie Z, Wei W, Gao GF  | title = Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B | journal = Cell | volume = 177 | issue = 6 | pages = 1553–1565.e16 | date = May 2019 | pmid = 31104841 | pmc = 7111318 | doi = 10.1016/j.cell.2019.04.035 }}</ref> However, the specific function for Vaccinia virus has not yet been elucidated.

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Huang WC, Havel JJ, Zhau HE, Qian WP, Lue HW, Chu CY, Nomura T, Chung LW  | title = Beta2-microglobulin signaling blockade inhibited androgen receptor axis and caused apoptosis in human prostate cancer cells | journal = Clinical Cancer Research | volume = 14 | issue = 17 | pages = 5341–5347 | date = September 2008 | pmid = 18765525 | pmc = 3032570 | doi = 10.1158/1078-0432.CCR-08-0793 }}
* {{cite journal | vauthors = Huang WC, Wu D, Xie Z, Zhau HE, Nomura T, Zayzafoon M, Pohl J, Hsieh CL, Weitzmann MN, Farach-Carson MC, Chung LW  | title = beta2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis | journal = Cancer Research | volume = 66 | issue = 18 | pages = 9108–9116 | date = September 2006 | pmid = 16982753 | doi = 10.1158/0008-5472.CAN-06-1996 | doi-access = free }}
* {{cite journal | vauthors = Winchester JF, Salsberg JA, Levin NW | title = Beta-2 microglobulin in ESRD: an in-depth review | journal = Advances in Renal Replacement Therapy | volume = 10 | issue = 4 | pages = 279–309 | date = October 2003 | pmid = 14681859 | doi = 10.1053/j.arrt.2003.11.003 }}
* {{cite journal | vauthors = Krangel MS, Orr HT, Strominger JL | title = Assembly and maturation of HLA-A and HLA-B antigens in vivo | journal = Cell | volume = 18 | issue = 4 | pages = 979–991 | date = December 1979 | pmid = 93026 | doi = 10.1016/0092-8674(79)90210-1 | doi-access = free }}
* {{cite journal | vauthors = Okon M, Bray P, Vucelić D | title = 1H NMR assignments and secondary structure of human beta 2-microglobulin in solution | journal = Biochemistry | volume = 31 | issue = 37 | pages = 8906–8915 | date = September 1992 | pmid = 1390678 | doi = 10.1021/bi00152a030 }}
* {{cite journal | vauthors = Guo HC, Jardetzky TS, Garrett TP, Lane WS, Strominger JL, Wiley DC | title = Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle | journal = Nature | volume = 360 | issue = 6402 | pages = 364–366 | date = November 1992 | pmid = 1448153 | doi = 10.1038/360364a0 | s2cid = 4324984 | bibcode = 1992Natur.360..364G }}
* {{cite journal | vauthors = Gattoni-Celli S, Kirsch K, Timpane R, Isselbacher KJ | title = 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 | journal = Cancer Research | volume = 52 | issue = 5 | pages = 1201–1204 | date = March 1992 | pmid = 1737380 }}
* {{cite journal | vauthors = Saper MA, Bjorkman PJ, Wiley DC | title = Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution | journal = Journal of Molecular Biology | volume = 219 | issue = 2 | pages = 277–319 | date = May 1991 | pmid = 2038058 | doi = 10.1016/0022-2836(91)90567-P }}
* {{cite journal | vauthors = Caruana RJ, Lobel SA, Leffell MS, Campbell H, Cheek PL | title = Tumor necrosis factor, interleukin-1 and beta 2-microglobulin levels in chronic hemodialysis patients | journal = The International Journal of Artificial Organs | volume = 13 | issue = 12 | pages = 794–798 | date = December 1990 | pmid = 2289831 | doi = 10.1177/039139889001301205 | s2cid = 24952854 }}
* {{cite journal | vauthors = Connors LH, Shirahama T, Skinner M, Fenves A, Cohen AS | title = In vitro formation of amyloid fibrils from intact beta 2-microglobulin | journal = Biochemical and Biophysical Research Communications | volume = 131 | issue = 3 | pages = 1063–1068 | date = September 1985 | pmid = 2413854 | doi = 10.1016/0006-291X(85)90198-6 }}
* {{cite journal | vauthors = Hochman JH, Shimizu Y, DeMars R, Edidin M | title = Specific associations of fluorescent beta-2-microglobulin with cell surfaces. The affinity of different H-2 and HLA antigens for beta-2-microglobulin | journal = Journal of Immunology | volume = 140 | issue = 7 | pages = 2322–2329 | date = April 1988 | pmid = 2450918 | doi = 10.4049/jimmunol.140.7.2322 | s2cid = 34035543 | doi-access = free }}
* {{cite journal | vauthors = Homma N, Gejyo F, Isemura M, Arakawa M | title = Collagen-binding affinity of beta-2-microglobulin, a preprotein of hemodialysis-associated amyloidosis | journal = Nephron | volume = 53 | issue = 1 | pages = 37–40 | year = 1989 | pmid = 2674742 | doi = 10.1159/000185699 }}
* {{cite journal | vauthors = Bataille R, Grenier J, Commes T | title = In vitro production of beta 2 microglobulin by human myeloma cells | journal = Cancer Investigation | volume = 6 | issue = 3 | pages = 271–277 | year = 1988 | pmid = 3048575 | doi = 10.3109/07357908809080649 }}
* {{cite journal | vauthors = Hönig R, Marsen T, Schad S, Barth C, Pollok M, Baldamus CA | title = Correlation of beta-2-microglobulin concentration changes to changes of distribution volume | journal = The International Journal of Artificial Organs | volume = 11 | issue = 6 | pages = 459–464 | date = November 1988 | pmid = 3060434 }}
* {{cite journal | vauthors = Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC | title = Structure of the human class I histocompatibility antigen, HLA-A2 | journal = Nature | volume = 329 | issue = 6139 | pages = 506–512 | year = 1987 | pmid = 3309677 | doi = 10.1038/329506a0 | s2cid = 4373217 | bibcode = 1987Natur.329..506B }}
* {{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 = Journal of Immunology | volume = 139 | issue = 9 | pages = 3132–3138 | date = November 1987 | pmid = 3312414 | doi = 10.4049/jimmunol.139.9.3132 | s2cid = 38290153 | doi-access = free }}
* {{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 = 4811–4822 | date = November 1973 | pmid = 4586824 | doi = 10.1021/bi00748a001 }}
* {{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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 11 | pages = 6613–6617 | date = November 1981 | pmid = 6171820 | pmc = 349099 | doi = 10.1073/pnas.78.11.6613 | doi-access = free | bibcode = 1981PNAS...78.6613S }}
* {{cite journal | vauthors = Momoi T, Suzuki M, Titani K, Hisanaga S, Ogawa H, Saito A | title = Amino acid sequence of a modified beta 2-microglobulin in renal failure patient urine and long-term dialysis patient blood | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 236 | issue = 2 | pages = 135–144 | date = May 1995 | pmid = 7554280 | doi = 10.1016/0009-8981(95)06039-G }}
* {{cite journal | vauthors = Collins EJ, Garboczi DN, Karpusas MN, Wiley DC | title = The three-dimensional structure of a class I major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 4 | pages = 1218–1221 | date = February 1995 | pmid = 7862664 | pmc = 42670 | doi = 10.1073/pnas.92.4.1218 | doi-access = free | bibcode = 1995PNAS...92.1218C }}
* {{cite journal | vauthors = Matoba R, Okubo K, Hori N, Fukushima A, Matsubara K | title = The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression | journal = Gene | volume = 146 | issue = 2 | pages = 199–207 | date = September 1994 | pmid = 8076819 | doi = 10.1016/0378-1119(94)90293-3 }}
* {{cite journal | vauthors = Wang Z, Cao Y, Albino AP, Zeff RA, Houghton A, Ferrone S | title = Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA | journal = The Journal of Clinical Investigation | volume = 91 | issue = 2 | pages = 684–692 | date = February 1993 | pmid = 8432869 | pmc = 288010 | doi = 10.1172/JCI116249 }}
{{Refend}}

== External links ==
* {{MeshName|beta+2-Microglobulin}}
* {{UCSC gene info|B2M}}
* {{PDBe-KB2|P61769|Beta-2 microglobulin}}

{{PDB Gallery|geneid=567}}
{{Beta globulins}}
{{Amyloidosis}}

{{DEFAULTSORT:Beta-2 Microglobulin}}
[[Category:Proteins]]
[[Category:Immune system]]