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  • GENE_NAME : CD20

    CD_NAME : CD20

    DESC: membrane-spanning 4-domains, subfamily A, member 1
    OTH_NAMES: B1; Bp35; MS4A2
    CLONE_NAME ISO_TYPE SUBMITTER AVAILABLE_FROM
    2H7 IgG2b  Clark  BD Biosciences
    L26 IgG2ak  Johansson  AbD Serotec
    L27 IgG1  Ishii  BD Biosciences
    2H7 IgG2b  Clark  BioLegend
    2H7 IgG2b  Clark  AbD Serotec
    2H7 IgG2b  Clark  eBioscience
  • CLONE_NAME ISO_TYPE SUBMITTER AVAILABLE_FROM
    1F5 IgG2a  Clark 
    2H7 IgG2b  Clark  BD Biosciences
    93-1B3 IgG1  Vilella 
    109-3C2 (weak) IgG3  Vilella 
    B1 IgG2a  Stashenko 
    B9E9 IgG2a  van Agthoven 
    B-B6 IgM  Wijdenes 
    B-C1 IgM  Gallart 
    B-H20 IgG2a Vermot-Desroches
    B-ly1 IgG1  Poppema 
    BLA.36 IgG3  Imam 
    CAT13.7H8 IgG1  Hadam 
    D2-1H4-1 IgG1  Hekman 
    D2-1H4-2a IgG2a  Hekman 
    D2-1H4-2b IgG2b  Hekman 
    F4B-13C6 IgM  Poncelet 
    FB1 IgG2a  Nozawa 
    G28-2 IgG3  Ledbetter 
    HB13a IgM  Tedder 
    HB13c IgG1  Tedder 
    HB13g IgM  Tedder 
    HB13h IgG1  Tedder 
    HI47 IgG3  Chen 
    L26 IgG2ak  Johansson  AbD Serotec
    L27 IgG1  Ishii  BD Biosciences
    LN8 IgG3  Ernst 
    MD20.2 IgM  van der Schoot 
    MEM-97 IgG1  Horejsi 
    NU-B2 IgG2b  Yokoyama 
    PDR78 IgG3  Pulford 
    1632-1; EP459Y IgG Frolkis
    2H7 IgG2b  Clark  BioLegend
    2H7 IgG2b  Clark  AbD Serotec
    2H7 IgG2b  Clark  eBioscience
  • STRUCTURE


    CD20 is a type III integral phosphoprotein belonging to the membrane-spanning 4A family.1-2 CD20 displays 4 transmembrane regions and potentially two extracellular loops, although the evidence for the smaller one is contradictory. 2-4 Both N- and C-terminal domains are located in the cytoplasm. The intracellular parts of CD20 contain several residues that can be phosphorylated.1-3

    1. Teeling JL, Mackus WJ, Wiegman LJ, van den Brakel JH, Beers SA, French RR, van Meerten T, Ebeling S, Vink T, Slootstra JW, Parren PW, Glennie MJ, van de Winkel JG. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol. 2006;177:362-71.

    2. Stamenkovic I, Seed B. Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein. J Exp Med. 1988;167:1975-80.

    3. Beers SA, Chan CH, French RR, Cragg MS, Glennie MJ. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol. 2010;47:107-14.

    4. Polyak MJ, Tailor SH, Deans JP. Identification of a cytoplasmic region of CD20 required for its redistribution to a detergent-insoluble membrane compartment. J Immunol. 1998;161:3242-8.

  • LIGANDS


    Extracellular

    No ligands have been described.1 However, it interacts in cis with itself forming multimers and it also associates with the BCR, CD40 and MHC class II.2-4 It potentially interacts with MHC class I, CD53, CD81 and CD82.5

    Intracellular

    CD20 can be immunoprecipitated together with phosphoproteins and calmodulin-binding proteins.2 In particular, CD20 has been found to be associated with lyn, lck, fyn and PAG.6-7

    1. Beers SA, Chan CH, French RR, Cragg MS, Glennie MJ. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol. 2010;47:107-14..

    2. Polyak MJ, Li H, Shariat N, Deans JP. CD20 homo-oligomers physically associate with the B cell antigen receptor. Dissociation upon receptor engagement and recruitment of phosphoproteins and calmodulin-binding proteins. J Biol Chem. 2008;283:18545-52.

    3. Buschow SI, van Balkom BW, Aalberts M, Heck AJ, Wauben M, Stoorvogel W. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunol Cell Biol. 2010;88:851-6.

    4. Léveillé C, AL-Daccak R, Mourad W. CD20 is physically and functionally coupled to MHC class II and CD40 on human B cell lines. Eur J Immunol. 1999;29:65-74.

    5. Szöllósi J, Horejsí V, Bene L, Angelisová P, Damjanovich S. 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. J Immunol. 1996;157:2939-46.

    6. Deans JP, Kalt L, Ledbetter JA, Schieven GL, Bolen JB, Johnson P. 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. J Biol Chem. 1995;270:22632-8.

    7. Deans JP, Li H, Polyak MJ. CD20-mediated apoptosis: signalling through lipid rafts. Immunology. 2002;107:176-82.


  • GENE_NAME : CD20

    CD_NAME : CD20

    CD20 is widely expressed on B cells during B cell development starting on early pre-B cells. CD20 is not present on plasma cells. 1 A small subset of T cells, accounting for 3-5% of T cells, displays moderate levels of CD20.2

    1. Tedder TF, Engel P. CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today. 1994;15:450-4.

    2. Schuh E, Berer K, Mulazzani M, Feil K, Meinl I, Lahm H, Krane M, Lange R, Pfannes K, Subklewe M, Gürkov R, Bradl M, Hohlfeld R, Kümpfel T, Meinl E, Krumbholz M. Features of Human CD3+CD20+ T Cells. J Immunol. 2016;197:1111-7.


  • GENE_NAME : CD20

    CD_NAME : CD20

    Although there are still no clues of its ligands, the role of CD20 has been studied in several publications. In particular, there are many evidences indicating that CD20 regulates the calcium influx and therefore calcium cytoplasmic levels.1-3 Through this calcium influx, CD20 may be able to control the cell growth.3 In particular, CD20 functions downstream of the BCR and its role is tied to the expression of this receptor.1,4-6 In addition, CD20 also regulates B cell activation.7

    1. Li H, Ayer LM, Lytton J, Deans JP. Store-operated cation entry mediated by CD20 in membrane rafts. J Biol Chem. 2003;278:42427-34.

    2. Bubien JK, Zhou LJ, Bell PD, Frizzell RA, Tedder TF. Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes. J Cell Biol. 1993;121:1121-32.

    3. Kanzaki M, Shibata H, Mogami H, Kojima I. Expression of calcium-permeable cation channel CD20 accelerates progression through the G1 phase in Balb/c 3T3 cells. J Biol Chem. 1995;270:13099-104.

    4. Uchida J, Lee Y, Hasegawa M, Liang Y, Bradney A, Oliver JA, Bowen K, Steeber DA, Haas KM, Poe JC, Tedder TF. Mouse CD20 expression and function. Int Immunol. 2004;16:119-29.

    5. Polyak MJ, Li H, Shariat N, Deans JP. CD20 homo-oligomers physically associate with the B cell antigen receptor. Dissociation upon receptor engagement and recruitment of phosphoproteins and calmodulin-binding proteins. J Biol Chem. 2008;283:18545-52.

    6. Walshe CA, Beers SA, French RR, Chan CH, Johnson PW, Packham GK, Glennie MJ, Cragg MS. Induction of cytosolic calcium flux by CD20 is dependent upon B Cell antigen receptor signaling. J Biol Chem. 2008;283:16971-84.

    7. Golay JT, Clark EA, Beverley PC. The CD20 (Bp35) antigen is involved in activation of B cells from the G0 to the G1 phase of the cell cycle. J Immunol. 1985;135:3795-801.


  • GENE_NAME : CD20

    CD_NAME : CD20

    Cell marker

    Given its expression in cells of the B lineage, CD20 can be used for diagnosis, classification and prognosis of lymphoid malignancies. 1 For instance, CD20 expression has been linked to a particular survival in CLL and adult B-cell acute lymphoblastic leukemia. 2-4

    1. van Dongen JJ, Lhermitte L, Böttcher S, Almeida J, van der Velden VH, Flores-Montero J, Rawstron A, Asnafi V, Lécrevisse Q, Lucio P, Mejstrikova E, Szczepański T, Kalina T, de Tute R, Brüggemann M, Sedek L, Cullen M, Langerak AW, Mendonça A, Macintyre E, Martin-Ayuso M, Hrusak O, Vidriales MB, Orfao A; EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708). EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012;26:1908-75.

    2. Yang S, Wang J, Zhao T, Jia J, Zhu H, Jiang H, Lu J, Jiang B, Shi H, Liu Y, Lai Y, Xu L, Huang X, Jiang Q. CD20 expression sub-stratifies standard-risk patients with B cell precursor acute lymphoblastic leukemia. Oncotarget. 2017;8:105397-105406.

    3. Fang C, Zhuang Y, Wang L, Fan L, Wu YJ, Zhang R, Zou ZJ, Zhang LN, Yang S, Xu W, Li JY. High levels of CD20 expression predict good prognosis in chronic lymphocytic leukemia. Cancer Sci. 2013;104:996-1001.

    4. Esteban RE, Christianne B, Alvaro A, Roberta DG. Prognostic Effect of CD20 Expression in Adult B-cell Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2018. pii: S2152-2650.

    Therapeutic

    Due to the characteristics of CD20, several monoclonal antibodies targeting this antigen are currently being used for therapy of hematologic malignancies or autoimmune diseases.

    The prototype of anti-CD20 monoclonal antibodies is Rituxan (rituximab) which was approved by the FDA in 1997 for the treatment of B-cell non-hodkin’s lymphoma.1 Since then, new indications for Rituxan treatment has been found including CLL, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis.2 Rituximab opened a new era for immunotherapy in lymphomas as it was the first monoclonal antibody approved for their treatment.1 Other anti-CD20 antibodies approved by the FDA are Gazyva3, Arzerra 4, Zevalin5 or Bexxar.6

    CAR T cell technology has also been developed targeting CD20, but has not been approved by the FDA yet. Phase II clinical trials using CARs are being performed for B cell malignancies.7-8 Effective results of CAR T cells against CD20 have already been reported in the area of lymphomas. 10

    1. Molina A. A decade of rituximab: improving survival outcomes in non-Hodgkin's lymphoma. Annu Rev Med. 2008;59:237-50.

    2. U.S. Food and Drug Administration [internet]. 23/07/2015. Rituximab. Available from: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109106.htm.

    3. U.S. Food and Drug Administration [internet]. 26/06/2016. Obinutuzumab. Available from:https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109106.htm.

    4. U.S. Food and Drug Administration [internet]. 07/09/2015. Arzerra. Available from: https://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm379961.htm.

    5. U.S. Food and Drug Administration [internet]. 08/12/2005. Drug Approval Package. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/125019_00 00_zevalintoc.cfm.

    6. U.S. Food and Drug Administration [internet]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125011s102lbl.pdf.

    7. ClinicalTrials.gov (NCT02710149) A Clinical Research of CD20-Targeted CAR-T in B Cell Malignancies. U.S. National Institutes of Health.

    8. ClinicalTrials.gov (NCT03207178) Sequential Infusion of Anti-CD19 and Anti-CD20 CAR-T Cells Against Relapsed and Refractory B-cell Lymphoma. U.S. National Institutes of Health.

    9. ClinicalTrials.gov (NCT03277729) A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas. U.S. National Institutes of Health.

    10. Zhang WY, Wang Y, Guo YL, Dai HR, Yang QM, Zhang YJ, Zhang Y, Chen MX, Wang CM, Feng KC, Li SX, Liu Y, Shi FX, Luo C, Han WD. Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Signal Transduct Target Ther. 2016;1:16002.


  • GENE_NAME : CD20

    CD_NAME : CD20

    GENERAL_INFORMATION

    NCBI_NAME CD20
    NCBI_OTHER_NAME B1; Bp35; MS4A2
    SWISS_NAMES CD20_HUMAN
    DESC membrane-spanning 4-domains, subfamily A, member 1

    LOCUS_INFO_LINKS

    HGNC_LOCUS_TAG: 7315
    ONLINE_MENDELIAN_INHERITANCE: 112210
    NCBI_HOMOLOGENE: 7259
    NCBI_MAP: 11q12-q13.1
    NCBI_ENTRE_GENE_ENTRY: 931
    GENE_SIZE: 14974
    EN_GE_EN:
    MRNA_SEQ_LENGTH: 1653
    PRCORENC: 147 to 1040
    ENTREN: ENST00000345732
    PROTEIN_LENGTH_NCBI_REFSEQ: 297
    NCBI_REF_SEF_ENTRY: NP_068769.2 , 23110987
    PROTEIN_LENGTH_SWISPROT: 297
    ENSEMBLE_PROT_ENTRY: ENSP00000314620
    PR_MO_WEIGHT: 33077
    SWPROT_PROTEIN_ENTRY: CD20_HUMAN , P11836
    PR_SW_PR: 5.04
    IPI_NUMBER: IPI00007880
    NCBI_CONSV_DOMAINS: 23110987
    ENSM_NUMBER: P11836

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