CD20

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Membrane-spanning 4-domains, subfamily A, member 1

Rendering based on PDB 1S8B.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols MS4A1 ; B1; Bp35; CD20; CVID5; LEU-16; MS4A2; S7
External IDs OMIM112210 MGI88321 HomoloGene7259 ChEMBL: 2058 GeneCards: MS4A1 Gene
RNA expression pattern
PBB GE MS4A1 210356 x at tn.png
PBB GE MS4A1 217418 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 931 12482
Ensembl ENSG00000156738 ENSMUSG00000024673
UniProt P11836 P19437
RefSeq (mRNA) NM_021950 NM_007641
RefSeq (protein) NP_068769 NP_031667
Location (UCSC) Chr 11:
60.22 – 60.24 Mb
Chr 19:
11.25 – 11.27 Mb
PubMed search [1] [2]

B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase (CD45R+, CD117+) and progressively increasing in concentration until maturity.[1]

In humans CD20 is encoded by the MS4A1 gene.[2][3]

This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This gene encodes a B-lymphocyte surface molecule that plays a role in the development and differentiation of B-cells into plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants that encode the same protein.[3]

Function[edit]

The protein has no known natural ligand[4] and its function is to enable optimal B-cell immune response, specifically against T-independent antigens.[5] It is suspected that it acts as a calcium channel in the cell membrane.

Expression[edit]

CD20 is expressed on all stages of B cell development except the first and last; it is present from late pro-B cells through memory cells, but not on either early pro-B cells or plasma blasts and plasma cells.[6][7] It is found on B-cell lymphomas, hairy cell leukemia, B-cell chronic lymphocytic leukemia, and melanoma cancer stem cells.[8]

Immunohistochemistry can be used to determine the presence of CD20 on cells in histological tissue sections. Because CD20 remains present on the cells of most B-cell neoplasms, and is absent on otherwise similar appearing T-cell neoplasms, it can be very useful in diagnosing conditions such as B-cell lymphomas and leukaemias. However, the presence or absence of CD20 in such tumours is not relevant to prognosis, with the progression of the disease being much the same in either case. CD20 positive cells are also sometimes found in cases of Hodgkins disease, myeloma, and thymoma.[9]

Antibody FMC7 appears to recognise a conformational variant of CD20[10][11] also known as the FMC7 antigen.[12]

Clinical significance[edit]

CD20 is the target of the monoclonal antibodies (mAb) rituximab, Ibritumomab tiuxetan, and tositumomab, which are all active agents in the treatment of all B cell lymphomas and leukemias.

The anti-CD20 mAB Ofatumumab (Genmab) was approved by FDA in Oct 2009 for Chronic lymphocytic leukemia.

Additional anti-CD20 antibody therapeutics under development (phase II or III clinical trials in 2008) include :

B cells, CD20, and diabetes mellitus[edit]

A link between the immune system's B cells and diabetes mellitus has been determined.[15] In cases of obesity, the presence of fatty tissues surrounding the body's major organ systems results in cell necrosis and insulin desensitivity along the boundary between them. Eventually, the contents of fat cells that would otherwise have been digested by insulin are shed into the bloodstream. An inflammation response that mobilizes both T and B cells results in the creation of 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 desensitivity 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 obesity be reclassify as an autoimmune disease rather than a purely metabolic one and focus treatment for it on immune system modulation.[15]

References[edit]

  1. ^ Hardy, Richard (2008). "Chapter 7: B Lymphocyte Development and Biology". In Paul, William. Fundamental Immunology (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 237–269. ISBN 0-7817-6519-6. 
  2. ^ Tedder TF, Streuli M, Schlossman SF, Saito H (Mar 1988). "Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface antigen of human B lymphocytes". Proc Natl Acad Sci U S A 85 (1): 208–12. doi:10.1073/pnas.85.1.208. PMC 279513. PMID 2448768. 
  3. ^ a b "Entrez Gene: MS4A1 membrane-spanning 4-domains, subfamily A, member 1". 
  4. ^ Cragg MS, Walshe CA, Ivanov AO, Glennie MJ (2005). "The biology of CD20 and its potential as a target for mAb therapy". Curr. Dir. Autoimmun. Current Directions in Autoimmunity 8: 140–74. doi:10.1159/000082102. ISBN 3-8055-7851-2. PMID 15564720. 
  5. ^ Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IA, Dolman KM, Beaumont T, Tedder TF, van Noesel CJ, Eldering E, van Lier RA (January 2010). "CD20 deficiency in humans results in impaired T cell-independent antibody responses". J. Clin. Invest. 120 (1): 214–22. doi:10.1172/JCI40231. PMC 2798692. PMID 20038800. 
  6. ^ Walport M, Murphy K, Janeway C, Travers PJ (2008). Janeway's Immunobiology (7th ed.). New York: Garland Science. ISBN 0-8153-4123-7. 
  7. ^ Bonilla FA, Bona CA (1996). "5". Textbook of Immunology. Boca Raton: CRC. p. 102. ISBN 3-7186-0596-1. 
  8. ^ Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (October 2005). "A tumorigenic subpopulation with stem cell properties in melanomas". Cancer Res. 65 (20): 9328–37. doi:10.1158/0008-5472.CAN-05-1343. PMID 16230395. 
  9. ^ Cooper K, Anthony Leong AS-Y (2003). Manual of diagnostic antibodies for immunohistology (2nd ed.). London: Greenwich Medical Media. ISBN 1-84110-100-1. 
  10. ^ Polyak MJ, Ayer LM, Szczepek AJ, Deans JP (July 2003). "A cholesterol-dependent CD20 epitope detected by the FMC7 antibody". Leukemia 17 (7): 1384–9. doi:10.1038/sj.leu.2402978. PMID 12835728. 
  11. ^ Serke S, Schwaner I, Yordanova M, Szczepek A, Huhn D (April 2001). "Monoclonal antibody FMC7 detects a conformational epitope on the CD20 molecule: evidence from phenotyping after rituxan therapy and transfectant cell analyses". Cytometry 46 (2): 98–104. doi:10.1002/cyto.1071. PMID 11309819. 
  12. ^ Deans JP, Polyak MJ (February 2008). "FMC7 is an epitope of CD20". Blood 111 (4): 2492; author reply 2493–4. doi:10.1182/blood-2007-11-126243. PMID 18263793. 
  13. ^ http://www.news-medical.net/news/20100615/Trubion-announces-Pfizers-decision-to-discontinue-development-of-TRU-015-for-RA.aspx
  14. ^ Note: information included in this article only found in table present in print version of article. K. John Morrow Jr (2008-06-15). "Methods for Maximizing Antibody Yields". Genetic Engineering & Biotechnology News (Mary Ann Liebert, Inc.). p. 36. Retrieved 2008-07-06. 
  15. ^ a b Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch HM, Engleman EG (April 2011). "B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies". Nat Med 17 (5): 610–7. doi:10.1038/nm.2353. PMC 3270885. PMID 21499269. Lay summaryStanford School of Medicine. 

Further reading[edit]

External links[edit]