CD19

CD19 molecule
Identifiers
Symbols CD19 ; B4; CVID3
External IDs OMIM: 107265 MGI: 88319 HomoloGene: 1341 GeneCards: CD19 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 930 12478
Ensembl ENSG00000177455 ENSMUSG00000030724
UniProt P15391 P25918
RefSeq (mRNA) NM_001178098 NM_009844
RefSeq (protein) NP_001171569 NP_033974
Location (UCSC) Chr 16:
28.93 – 28.94 Mb		 Chr 7:
126.41 – 126.41 Mb
PubMed search

B-lymphocyte antigen CD19, also known as CD19 (Cluster of Differentiation 19), is a protein that in humans is encoded by the CD19 gene.[1][2] 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.[1]

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 living 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.[7][8]

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.[9] Since 2011 treatments targeting CD19 have begun to enter trials.[10][11][12] 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 [13][14]

CD19 has also been implicated in autoimmune diseases and may be a useful treatment target.[15]

References

  1. 1 2 "Entrez Gene: CD19 CD19 molecule".
  2. ↑ 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.
  3. 1 2 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.
  4. 1 2 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.
  5. 1 2 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ A Phase I Study of CD19 Specific T Cells in CD19 Positive Malignancy
  11. ↑ "CAR T cells for leukemia and more?". AACR Annual Meeting, Chicago, Illinois. American Association for Cancer Research. April 3, 2012. Retrieved 17 April 2013.
  12. ↑ Coghlan, Andy (26 March 2013) Gene therapy cures leukaemia in eight days The New Scientist, Retrieved 15 April 2013
  13. ↑ 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.
  14. ↑ B-cell lymphoma discovery could lead to new treatments - Cancer Research UK news article, April 2012
  15. ↑ 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

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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