CD19

O CD19 (clúster de diferenciación 19) ou antíxeno de linfocito B CD19 é unha proteína de membrana que se encontra na superficie dos linfocitos B, codificada polo xene CD19 humano, situado no cromosoma 16.

Función

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. This 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.

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.

Interaccións

CD19 has been shown to interact with:

• CD81,
• CD82
• Complement receptor 2, and
• VAV2.

En enfermidades

Mutations in CD19 are associated with severe immunodeficiency syndromes characterized by diminished antibody production.

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. More recently, treatments targeting CD19 have begun to enter trials. 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 stabilising the concentrations of the MYC oncoprotein. This suggests that CD19 and its downstream signalling may be a more attractive therapeutic target than suspected

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

Véxase tamén

Outras lecturas

• Goldsby, Richard A.; Kindt, Thomas J.; Osborne, Barbara A. (2006). Kuby Immunology. San Francisco: W. H. Freeman. ISBN 0-7167-8590-0. 

{{PBB_Further_reading | citations =

• Ishikawa H, Tsuyama N, Mahmoud MS; et al. (2003). "CD19 expression and growth inhibition of tumours in human multiple myeloma.". Leuk. Lymphoma 43 (3): 613–6. PMID 12002767. doi:10.1080/10428190290012146. 
• 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. PMID 1370948. doi:10.1007/BF00189519. 
• Carter RH, Fearon DT (1992). "CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes.". Science 256 (5053): 105–7. PMID 1373518. doi:10.1126/science.1373518. 
• Kozmik Z, Wang S, Dörfler P; et al. (1992). "The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP.". Mol. Cell. Biol. 12 (6): 2662–72. PMC 364460. PMID 1375324. 
• Bradbury LE, Kansas GS, Levy S; et al. (1992). "The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules.". J. Immunol. 149 (9): 2841–50. PMID 1383329. 
• Matsumoto AK, Kopicky-Burd J, Carter RH; et al. (1991). "Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19.". J. Exp. Med. 173 (1): 55–64. PMC 2118751. PMID 1702139. doi:10.1084/jem.173.1.55. 
• Zhou LJ, Ord DC, Hughes AL, Tedder TF (1991). "Structure and domain organization of the CD19 antigen of human, mouse, and guinea pig B lymphocytes. Conservation of the extensive cytoplasmic domain.". J. Immunol. 147 (4): 1424–32. PMID 1714482. 
• Stamenkovic I, Seed B (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.". J. Exp. Med. 168 (3): 1205–10. PMC 2189043. PMID 2459292. doi:10.1084/jem.168.3.1205. 
• Ord DC, Edelhoff S, Dushkin H; et al. (1994). "CD19 maps to a region of conservation between human chromosome 16 and mouse chromosome 7.". Immunogenetics 39 (5): 322–8. PMID 7513297. doi:10.1007/BF00189228. 
• Weng WK, Jarvis L, LeBien TW (1995). "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.". J. Biol. Chem. 269 (51): 32514–21. PMID 7528218. 
• Myers DE, Jun X, Waddick KG; et al. (1995). "Membrane-associated CD19-LYN complex is an endogenous p53-independent and Bc1-2-independent regulator of apoptosis in human B-lineage lymphoma cells.". Proc. Natl. Acad. Sci. U.S.A. 92 (21): 9575–9. PMC 40844. PMID 7568175. doi:10.1073/pnas.92.21.9575. 
• Chalupny NJ, Aruffo A, Esselstyn JM; et al. (1995). "Specific binding of Fyn and phosphatidylinositol 3-kinase to the B cell surface glycoprotein CD19 through their src homology 2 domains.". Eur. J. Immunol. 25 (10): 2978–84. PMID 7589101. doi:10.1002/eji.1830251040. 
• Tuscano JM, Engel P, Tedder TF; et al. (1996). "Involvement of p72syk kinase, p53/56lyn kinase and phosphatidyl inositol-3 kinase in signal transduction via the human B lymphocyte antigen CD22.". Eur. J. Immunol. 26 (6): 1246–52. PMID 8647200. doi:10.1002/eji.1830260610. 
• Carter RH, Doody GM, Bolen JB, Fearon DT (1997). "Membrane IgM-induced tyrosine phosphorylation of CD19 requires a CD19 domain that mediates association with components of the B cell antigen receptor complex.". J. Immunol. 158 (7): 3062–9. PMID 9120258. 
• Husson H, Mograbi B, Schmid-Antomarchi H; et al. (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. PMID 9178909. doi:10.1038/sj.onc.1201074. 
• Khine AA, Firtel M, Lingwood CA (1998). "CD77-dependent retrograde transport of CD19 to the nuclear membrane: functional relationship between CD77 and CD19 during germinal center B-cell apoptosis.". J. Cell. Physiol. 176 (2): 281–92. PMID 9648915. doi:10.1002/(SICI)1097-4652(199808)176:2<281::AID-JCP6>3.0.CO;2-K. 
• Thunberg U, Gidlöf C, Bånghagen M; et al. (1998). "HpaII polymerase chain reaction restriction fragment length polymorphism in the human CD19 gene on 16p11.". Hum. Hered. 48 (4): 230–1. PMID 9694255. doi:10.1159/000022806. 
• Horváth G, Serru V, Clay D; et al. (1998). "CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82.". J. Biol. Chem. 273 (46): 30537–43. PMID 9804823. doi:10.1074/jbc.273.46.30537. 
• Buhl AM, Cambier JC (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.". J. Immunol. 162 (8): 4438–46. PMID 10201980. 

Ligazóns externas

• Mapa dos antíxenos CD de ratos
• Mapa dos antíxenos CD humanos
• Nova patente sobre anticorpos que se unen a CD19