CD20
| MS4A1 | |||
|---|---|---|---|
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 11: 60.46 – 60.47 Mb | Chr 19: 11.23 – 11.24 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all
CD117+) and progressively increasing in concentration until maturity.[5]
In humans CD20 is encoded by the MS4A1 gene.[6][7]
This gene encodes a member of the
plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of the human MS4A1 gene results in at least three transcript variants (1 to 3) that encode the same protein.[7] Variants 1 and 2 are poorly translated due to inhibitory upstream open reading frames and stem-loop structures within their 5' untranslated regions. The relative abundance of translation-competent variant 3, as opposed to the poorly translated variants 1 and 2, may be a key determinant of CD20 levels in normal and malignant human B cells and their responses to CD20-directed immunotherapies. [8]
Function
The protein has no known natural
CXCL12) chemokine signaling and the molecular function of CD20 has been linked to the signaling propensity of B-cell receptor (BCR) in this context.[11]
Expression
CD20 is expressed on all stages of B cell development except the first and last; it is present from
lymphomas, hairy cell leukemia, B-cell chronic lymphocytic leukemia, and melanoma cancer stem cells.[14]
Antibody FMC7 (Flinders Medical Centre) appears to recognise a conformational variant of CD20[16][17] also known as the FMC7 antigen.[18]
Clinical significance
CD20 is the target of the
leukemias
, and B cell-mediated autoimmune diseases.
The anti-CD20 mAB ofatumumab (Genmab) was approved by FDA in October 2009 for chronic lymphocytic leukemia.
The anti-CD20 mAB obinutuzumab (Gazyva) was approved by FDA in November 2013 for chronic lymphocytic leukemia.
systemic lupus erythematosus were discontinued in 2010 due to an infection related safety risk.[19]
Although phase II trials for the use of
myalgic encephalomyelitis showed promising results, these could not be replicated in a large randomized controlled trial [20] and preliminary results from a Phase III trial were negative.[21]
Additional anti-CD20 antibody therapeutics under development (phase II or III clinical trials in 2008) include :
- systemic lupus erythematosus,
- Ocaratuzumab for follicular lymphoma and rheumatoid arthritis,
- TRU-015 (by Trubion), (discontinued in 2010[22])
- IMMU-106 (immune thrombocytopenia.
B cells, CD20, and diabetes mellitus
A link between the
antibodies against these cells, causing them to become less responsive to insulin by an as-yet-unknown mechanism and promoting hypertension, hypertriglyceridemia, and arteriosclerosis, hallmarks of the metabolic syndrome. Obese mice administered anti-B cell CD-20 antibodies, however, did not become less responsive to insulin and as a result, did not develop diabetes mellitus or the metabolic syndrome, the posited mechanism being that anti-CD20 antibodies rendered the T cell antibodies dysfunctional and therefore powerless to cause insulin insensitivity by a B cell antibody-modulated autoimmune response. The protection afforded by anti-CD-20 lasted approximately forty days—the time it takes the body to replenish its supply of B cells—after which repetition was necessary to restore it. Hence, it has been argued that diabetes mellitus be reclassified as an autoimmune disease rather than a purely metabolic one and focus treatment for it on immune system modulation.[25]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000156738 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024673 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ISBN 978-0-7817-6519-0.
- PMID 2448768.
- ^ a b "Entrez Gene: MS4A1 membrane-spanning 4-domains, subfamily A, member 1".
- S2CID 261620430.
- PMID 15564720.
- PMID 20038800.
- S2CID 49895265.
- ISBN 978-0-8153-4123-9.
- ISBN 978-3-7186-0596-5.
- PMID 16230395.
- ISBN 978-1-84110-100-2.
- PMID 12835728.
- PMID 11309819.
- PMID 18263793.
- ^ "Roche and Biogen Idec Announce Their Decision to Discontinue the ocrelizumab Clinical Development Programme in Patients with Rheumatoid Arthritis". investors.biogen.com. Retrieved 6 January 2022.
- S2CID 91186383.
- ^ "ME-studie med negative resultater". Dagens Medicin (in Norwegian). Retrieved 6 January 2022.
- ^ "Trubion announces Pfizer's decision to discontinue development of TRU-015 for RA". Trubion Pharmaceuticals, Inc. press release. 15 June 2010.
- Mary Ann Liebert, Inc. p. 36. Archived from the originalon 13 February 2009. Retrieved 6 July 2008.
- PMID 21499269.
- Krista Conger (17 April 2011). "Type-2 diabetes linked to autoimmune reaction in study". Stanford School of Medicine. Archived from the original on 6 May 2011.
- ^ "Diabetes Mellitus". The Lecturio Medical Concept Library. Retrieved 9 July 2021.
Further reading
- Macardle PJ, Nicholson IC (2003). "CD20". Journal of Biological Regulators and Homeostatic Agents. 16 (2): 136–138. PMID 12144126.
- Tamayose K, Sato N, Ando J, Sugimoto K, Oshimi K (December 2002). "CD3-negative, CD20-positive T-cell prolymphocytic leukemia: case report and review of the literature". American Journal of Hematology. 71 (4): 331–335. S2CID 23999423.
- Küster H, Zhang L, Brini AT, MacGlashan DW, Kinet JP (June 1992). "The gene and cDNA for the human high affinity immunoglobulin E receptor beta chain and expression of the complete human receptor". The Journal of Biological Chemistry. 267 (18): 12782–12787. PMID 1535625.
- Einfeld DA, Brown JP, Valentine MA, Clark EA, Ledbetter JA (March 1988). "Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains". The EMBO Journal. 7 (3): 711–717. PMID 2456210.
- Tedder TF, Disteche CM, Louie E, Adler DA, Croce CM, Schlossman SF, Saito H (April 1989). "The gene that encodes the human CD20 (B1) differentiation antigen is located on chromosome 11 near the t(11;14)(q13;q32) translocation site". Journal of Immunology. 142 (7): 2555–2559. S2CID 20030567.
- Tedder TF, Klejman G, Schlossman SF, Saito H (April 1989). "Structure of the gene encoding the human B lymphocyte differentiation antigen CD20 (B1)". Journal of Immunology. 142 (7): 2560–2568. S2CID 30587436.
- Loken MR, Shah VO, Dattilio KL, Civin CI (November 1987). "Flow cytometric analysis of human bone marrow. II. Normal B lymphocyte development". Blood. 70 (5): 1316–1324. PMID 3117132.
- Stamenkovic I, Seed B (June 1988). "Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein". The Journal of Experimental Medicine. 167 (6): 1975–1980. PMID 3260267.
- Bofill M, Janossy G, Janossa M, Burford GD, Seymour GJ, Wernet P, Kelemen E (March 1985). "Human B cell development. II. Subpopulations in the human fetus". Journal of Immunology. 134 (3): 1531–1538. S2CID 29484405.
- Deans JP, Kalt L, Ledbetter JA, Schieven GL, Bolen JB, Johnson P (September 1995). "Association of 75/80-kDa phosphoproteins and the tyrosine kinases Lyn, Fyn, and Lck with the B cell molecule CD20. Evidence against involvement of the cytoplasmic regions of CD20". The Journal of Biological Chemistry. 270 (38): 22632–22638. PMID 7545683.
- Valentine MA, Licciardi KA, Clark EA, Krebs EG, Meier KE (January 1993). "Insulin regulates serine/threonine phosphorylation in activated human B lymphocytes". Journal of Immunology. 150 (1): 96–105. S2CID 24522632.
- Bubien JK, Zhou LJ, Bell PD, Frizzell RA, Tedder TF (June 1993). "Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes". The Journal of Cell Biology. 121 (5): 1121–1132. PMID 7684739.
- Shirakawa T, Li A, Dubowitz M, Dekker JW, Shaw AE, Faux JA, et al. (June 1994). "Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor". Nature Genetics. 7 (2): 125–129. S2CID 24026689.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. PMID 8125298.
- Szepetowski P, Perucca-Lostanlen D, Gaudray P (June 1993). "Mapping genes according to their amplification status in tumor cells: contribution to the map of 11q13". Genomics. 16 (3): 745–750. PMID 8325649.
- Algino KM, Thomason RW, King DE, Montiel MM, Craig FE (July 1996). "CD20 (pan-B cell antigen) expression on bone marrow-derived T cells". American Journal of Clinical Pathology. 106 (1): 78–81. PMID 8701937.
- Szöllósi J, Horejsí V, Bene L, Angelisová P, Damjanovich S (October 1996). "Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY". Journal of Immunology. 157 (7): 2939–2946. S2CID 18389389.
- Kanzaki M, Lindorfer MA, Garrison JC, Kojima I (June 1997). "Activation of the calcium-permeable cation channel CD20 by alpha subunits of the Gi protein". The Journal of Biological Chemistry. 272 (23): 14733–14739. PMID 9169438.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. PMID 9373149.
External links
- CD20+antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- representations of the shape are found here and more detail here
- Human MS4A1 genome location and MS4A1 gene details page in the UCSC Genome Browser.
- Human MS4A2 genome location and MS4A2 gene details page in the UCSC Genome Browser.