CD19
B-lymphocyte antigen CD19, also known as CD19 (Cluster of Differentiation 19), is a protein that in humans is encoded by the CD19 gene.[5][6] It is found on the surface of B-cells, a type of white blood cell.
Function
Lymphocytes proliferate and differentiate in response to various concentrations of different antigens. The ability of the B cell to respond in a specific, yet sensitive manner to the various antigens is achieved with the use of low-affinity antigen receptors. The CD19 gene encodes a cell surface molecule that assembles with the antigen receptor of B lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation.[5]
CD19 is expressed on follicular dendritic cells and B cells. In fact, it is present on B cells from earliest recognizable B-lineage cells during development to B-cell blasts but is lost on maturation to plasma cells. It primarily acts as a B cell co-receptor in conjunction with CD21 and CD81. Upon activation, the cytoplasmic tail of CD19 becomes phosphorylated, which leads to binding by Src-family kinases and recruitment of PI-3 kinase.
As on T cells, several surface molecules form the antigen receptor and form a complex on B lymphocytes. The (almost) B cell-specific CD19 phosphoglycoprotein is one of these molecules. The others are CD21 and CD81. These surface immunoglobulin (sIg)-associated molecules facilitate signal transduction. On B cells, anti-immunoglobulin antibody mimicking exogenous antigen causes CD19 to bind to sIg and internalize with it. The reverse process has not been demonstrated, suggesting that formation of this receptor complex is antigen-induced. This molecular association has been confirmed by chemical studies.
Interactions
CD19 has been shown to interact with:
In disease
Mutations in CD19 are associated with severe immunodeficiency syndromes characterized by diminished antibody production.[11][12]
Since CD19 is a hallmark of B-cells, the protein has been used to diagnose cancers that arise from this type of cell - notably B-cell lymphomas.[13] Since 2011, anti-CD19 immunotoxin treatments targeting CD19 have begun to enter trials.[14][15][16][17] Most current experimental anti-CD19 drugs in development work by exploiting the presence of CD19 to direct treatment specifically towards B-cell cancers. However, it is now emerging that the protein plays an active role in driving the growth of these cancers, most intriguingly by stabilizing the concentrations of the MYC oncoprotein. This suggests that CD19 and its downstream signaling may be a more attractive therapeutic target than suspected [18][19]
CD19 has also been implicated in autoimmune diseases and may be a useful treatment target.[20]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000177455 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030724 – 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.
- ^ a b "Entrez Gene: CD19 CD19 molecule".
- ^ Tedder TF, Isaacs CM (Jul 1989). "Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes. A new member of the immunoglobulin superfamily". Journal of Immunology. 143 (2): 712–7. PMID 2472450.
- ^ a b Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF (Nov 1992). "The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules". Journal of Immunology. 149 (9): 2841–50. PMID 1383329.
- ^ a b Horváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E (Nov 1998). "CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82". The Journal of Biological Chemistry. 273 (46): 30537–43. doi:10.1074/jbc.273.46.30537. PMID 9804823.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ a b Imai T, Kakizaki M, Nishimura M, Yoshie O (Aug 1995). "Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82". Journal of Immunology. 155 (3): 1229–39. PMID 7636191.
- ^ Doody GM, Billadeau DD, Clayton E, Hutchings A, Berland R, McAdam S, Leibson PJ, Turner M (Nov 2000). "Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes". The EMBO Journal. 19 (22): 6173–84. doi:10.1093/emboj/19.22.6173. PMC 305817. PMID 11080163.
- ^ Pesando JM, Bouchard LS, McMaster BE (Dec 1989). "CD19 is functionally and physically associated with surface immunoglobulin". The Journal of Experimental Medicine. 170 (6): 2159–64. doi:10.1084/jem.170.6.2159. PMC 2189531. PMID 2479707.
- ^ van Zelm MC, Reisli I, van der Burg M, Castaño D, van Noesel CJ, van Tol MJ, Woellner C, Grimbacher B, Patiño PJ, van Dongen JJ, Franco JL (May 2006). "An antibody-deficiency syndrome due to mutations in the CD19 gene". The New England Journal of Medicine. 354 (18): 1901–12. doi:10.1056/NEJMoa051568. PMID 16672701.
- ^ Scheuermann RH, Racila E (Aug 1995). "CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy". Leukemia & Lymphoma. 18 (5–6): 385–97. doi:10.3109/10428199509059636. PMID 8528044.
- ^ A Phase I Study of CD19 Specific T Cells in CD19 Positive Malignancy
- ^ "CAR T cells for leukemia and more?". AACR Annual Meeting, Chicago, Illinois. American Association for Cancer Research. April 3, 2012. Retrieved 17 April 2013.
- ^ Coghlan, Andy (26 March 2013) Gene therapy cures leukaemia in eight days The New Scientist, Retrieved 15 April 2013
- ^ "NCI Dictionary of Cancer Terms". National Cancer Institute. Retrieved 2017-02-24.
- ^ Chung EY, Psathas JN, Yu D, Li Y, Weiss MJ, Thomas-Tikhonenko A (Jun 2012). "CD19 is a major B cell receptor-independent activator of MYC-driven B-lymphomagenesis". The Journal of Clinical Investigation. 122 (6): 2257–66. doi:10.1172/JCI45851. PMC 3366393. PMID 22546857.
- ^ B-cell lymphoma discovery could lead to new treatments - Cancer Research UK news article, April 2012
- ^ Fujimoto M, Sato S (Apr 2007). "B cell signaling and autoimmune diseases: CD19/CD22 loop as a B cell signaling device to regulate the balance of autoimmunity". Journal of Dermatological Science. 46 (1): 1–9. doi:10.1016/j.jdermsci.2006.12.004. PMID 17223015.
Further reading
- Goldsby, Richard A.; Kindt, Thomas J.; Osborne, Barbara A. (2006). Kuby Immunology. San Francisco: W. H. Freeman. ISBN 0-7167-8590-0.
- Ishikawa H, Tsuyama N, Mahmoud MS, Fujii R, Abroun S, Liu S, Li FJ, Kawano MM (Mar 2002). "CD19 expression and growth inhibition of tumours in human multiple myeloma". Leukemia & Lymphoma. 43 (3): 613–6. doi:10.1080/10428190290012146. PMID 12002767.
- Zhou LJ, Ord DC, Omori SA, Tedder TF (1992). "Structure of the genes encoding the CD19 antigen of human and mouse B lymphocytes". Immunogenetics. 35 (2): 102–11. doi:10.1007/BF00189519. PMID 1370948.
- Carter RH, Fearon DT (Apr 1992). "CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes". Science. 256 (5053): 105–7. doi:10.1126/science.1373518. PMID 1373518.
- Kozmik Z, Wang S, Dörfler P, Adams B, Busslinger M (Jun 1992). "The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP". Molecular and Cellular Biology. 12 (6): 2662–72. doi:10.1128/mcb.12.6.2662. PMC 364460. PMID 1375324.
- Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF (Nov 1992). "The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules". Journal of Immunology. 149 (9): 2841–50. PMID 1383329.
- Matsumoto AK, Kopicky-Burd J, Carter RH, Tuveson DA, Tedder TF, Fearon DT (Jan 1991). "Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19". The Journal of Experimental Medicine. 173 (1): 55–64. doi:10.1084/jem.173.1.55. PMC 2118751. PMID 1702139.
- Zhou LJ, Ord DC, Hughes AL, Tedder TF (Aug 1991). "Structure and domain organization of the CD19 antigen of human, mouse, and guinea pig B lymphocytes. Conservation of the extensive cytoplasmic domain". Journal of Immunology. 147 (4): 1424–32. PMID 1714482.
- Stamenkovic I, Seed B (Sep 1988). "CD19, the earliest differentiation antigen of the B cell lineage, bears three extracellular immunoglobulin-like domains and an Epstein-Barr virus-related cytoplasmic tail". The Journal of Experimental Medicine. 168 (3): 1205–10. doi:10.1084/jem.168.3.1205. PMC 2189043. PMID 2459292.
- Ord DC, Edelhoff S, Dushkin H, Zhou LJ, Beier DR, Disteche C, Tedder TF (1994). "CD19 maps to a region of conservation between human chromosome 16 and mouse chromosome 7". Immunogenetics. 39 (5): 322–8. doi:10.1007/BF00189228. PMID 7513297.
- Weng WK, Jarvis L, LeBien TW (Dec 1994). "Signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B cell precursors". The Journal of Biological Chemistry. 269 (51): 32514–21. PMID 7528218.
- Myers DE, Jun X, Waddick KG, Forsyth C, Chelstrom LM, Gunther RL, Tumer NE, Bolen J, Uckun FM (Oct 1995). "Membrane-associated CD19-LYN complex is an endogenous p53-independent and Bc1-2-independent regulator of apoptosis in human B-lineage lymphoma cells". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9575–9. doi:10.1073/pnas.92.21.9575. PMC 40844. PMID 7568175.
- Chalupny NJ, Aruffo A, Esselstyn JM, Chan PY, Bajorath J, Blake J, Gilliland LK, Ledbetter JA, Tepper MA (Oct 1995). "Specific binding of Fyn and phosphatidylinositol 3-kinase to the B cell surface glycoprotein CD19 through their src homology 2 domains". European Journal of Immunology. 25 (10): 2978–84. doi:10.1002/eji.1830251040. PMID 7589101.
- Tuscano JM, Engel P, Tedder TF, Agarwal A, Kehrl JH (Jun 1996). "Involvement of p72syk kinase, p53/56lyn kinase and phosphatidyl inositol-3 kinase in signal transduction via the human B lymphocyte antigen CD22". European Journal of Immunology. 26 (6): 1246–52. doi:10.1002/eji.1830260610. PMID 8647200.
- Carter RH, Doody GM, Bolen JB, Fearon DT (Apr 1997). "Membrane IgM-induced tyrosine phosphorylation of CD19 requires a CD19 domain that mediates association with components of the B cell antigen receptor complex". Journal of Immunology. 158 (7): 3062–9. PMID 9120258.
- Husson H, Mograbi B, Schmid-Antomarchi H, Fischer S, Rossi B (May 1997). "CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2". Oncogene. 14 (19): 2331–8. doi:10.1038/sj.onc.1201074. PMID 9178909.
- Khine AA, Firtel M, Lingwood CA (Aug 1998). "CD77-dependent retrograde transport of CD19 to the nuclear membrane: functional relationship between CD77 and CD19 during germinal center B-cell apoptosis". Journal of Cellular Physiology. 176 (2): 281–92. doi:10.1002/(SICI)1097-4652(199808)176:2<281::AID-JCP6>3.0.CO;2-K. PMID 9648915.
- Thunberg U, Gidlöf C, Bånghagen M, Sällström JF, Sundström C, Tötterman T (1998). "HpaII polymerase chain reaction restriction fragment length polymorphism in the human CD19 gene on 16p11". Human Heredity. 48 (4): 230–1. doi:10.1159/000022806. PMID 9694255.
- Horváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E (Nov 1998). "CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82". The Journal of Biological Chemistry. 273 (46): 30537–43. doi:10.1074/jbc.273.46.30537. PMID 9804823.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - Buhl AM, Cambier JC (Apr 1999). "Phosphorylation of CD19 Y484 and Y515, and linked activation of phosphatidylinositol 3-kinase, are required for B cell antigen receptor-mediated activation of Bruton's tyrosine kinase". Journal of Immunology. 162 (8): 4438–46. PMID 10201980.
External links
- Mouse CD Antigen Chart
- Human CD Antigen Chart
- Human CD19 genome location and CD19 gene details page in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.