Biology:Beta-2 microglobulin

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Short description: Component of MHC class I molecules

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells (excluding red blood cells).[1][2] In humans, the β2 microglobulin protein[3] is encoded by the B2M gene.[2][4]

Structure and function

Schematic representation of MHC class I

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 (5 genes in humans), MR1, the neonatal Fc receptor (FcRn), and Qa-1 (a form of alloantigen). Nevertheless, the β2 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.[5]


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.[6]

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.[7] However, with respect to multiple myeloma, the levels of β2 microglobulin may also be at the other end of the spectrum.[8] 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.[9] β2 microglobulin levels cannot, however, distinguish between monoclonal gammopathy of undetermined significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.[10][11]


Virus relevance

β2 microglobulin has been shown to be of high relevance for viral entry of Coxsackievirus A9 and Vaccinia virus (a Poxvirus).[12] For Coxsackievirus A9, it is likely that β2 microglobulin is required for the transport to plasma membrane of the identified receptor, the Human Neonatal Fc Receptor (FcRn).[13] However, the specific function for Vaccinia virus has not yet been elucidated.

References

  1. ↑ "Entrez Gene: Beta-2-microglobulin". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=567. 
  2. ↑ 2.0 2.1 "The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit". Journal of Immunology 139 (9): 3132–3138. November 1987. doi:10.4049/jimmunol.139.9.3132. PMID 3312414. 
  3. ↑ "The complete amino acid sequence of beta 2-microglobulin". Biochemistry 12 (24): 4811–4822. November 1973. doi:10.1021/bi00748a001. PMID 4586824. 
  4. ↑ "Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin". Proceedings of the National Academy of Sciences of the United States of America 78 (11): 6613–6617. November 1981. doi:10.1073/pnas.78.11.6613. PMID 6171820. Bibcode: 1981PNAS...78.6613S. 
  5. ↑ "Chapter 3: Iron, Heme, and Hemoglobin". Hematology: A Pathophysiologic Approach (1st ed.). Elsevier - Health Sciences Division. 2011. pp. 17–25. ISBN 978-0-323-04311-3. 
  6. ↑ "Beta-2-Microglobulin Levels in Human-Immunodeficiency Virus Infected Subjects". Medical Journal, Armed Forces India 53 (4): 251–254. October 1997. doi:10.1016/S0377-1237(17)30746-3. PMID 28769505. 
  7. ↑ Pignone M, Nicoll D; McPhee SJ (2004). Pocket guide to diagnostic tests (4th ed.). New York: McGraw-Hill. pp. 191. ISBN 0-07-141184-4. https://archive.org/details/isbn_9780071411844/page/191. 
  8. ↑ "Amyloidosis". https://www.lecturio.com/concepts/amyloidosis/. 
  9. ↑ "Chapter 111: Plasma Cell Disorders". Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill Professional. 2011. pp. 936–44. ISBN 978-0-07-174889-6. 
  10. ↑ "MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management". Hematology. American Society of Hematology. Education Program 2005: 340–345. 2005. doi:10.1182/asheducation-2005.1.340. PMID 16304401. 
  11. ↑ "Serum levels of beta 2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of undetermined significance". Blood 80 (9): 2433–2434. November 1992. doi:10.1182/blood.V80.9.2433.2433. PMID 1421418. 
  12. ↑ "Identification of β2 microglobulin, the product of B2M gene, as a Host Factor for Vaccinia Virus Infection by Genome-Wide CRISPR genetic screens". PLOS Pathogens 18 (12). December 2022. doi:10.1371/journal.ppat.1010800. PMID 36574441. 
  13. ↑ "Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B". Cell 177 (6): 1553–1565.e16. May 2019. doi:10.1016/j.cell.2019.04.035. PMID 31104841. 

Further reading



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