CD19

CD19
識別號
别名	CD19；, B4, CVID3, CD19 molecule
外部ID	OMIM：107265 MGI：88319 HomoloGene：1341 GeneCards：CD19
基因位置（人类）
染色体	16號染色體
终止	28,939,342 bp
基因位置（小鼠）
染色体	小鼠7号染色体
终止	126,014,061 bp
RNA表达模式
	查阅更多表达数据
基因本體
分子功能	• 血浆蛋白结合; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity;
細胞組分	• integral component of membrane; • 细胞膜; • integral component of plasma membrane; • 外排體; • 膜; • external side of plasma membrane; • 大分子复合体; • 脂筏模型;
生物學過程	• cellular defense response; • cell surface receptor signaling pathway; • regulation of immune response; • positive regulation of release of sequestered calcium ion into cytosol; • phosphatidylinositol phosphate biosynthetic process; • B cell receptor signaling pathway; • regulation of complement activation; • positive regulation of protein kinase B signaling; • B-1 B cell differentiation; • B cell proliferation involved in immune response; • immunoglobulin mediated immune response; • B cell mediated immunity; • positive regulation of phosphatidylinositol 3-kinase activity; • antigen receptor-mediated signaling pathway; • regulation of B cell receptor signaling pathway; • regulation of B cell activation; • 适应性免疫; • immune system process;
	Sources:Amigo / QuickGO
直系同源
	930
	12478
	ENSG00000177455
	ENSMUSG00000030724
	P15391
	P25918
	NM_001178098; NM_001770; NM_001385732
	NM_009844; NM_001357091
	NP_001171569; NP_001761
	NP_033974; NP_001344020
	維基數據
檢視/編輯人類	檢視/編輯小鼠

B淋巴細胞抗原CD19（B-lymphocyte antigen CD19），也稱為CD19分子（Cluster of Differentiation 19），B淋巴細胞表面抗原B4、T細胞表面抗原Leu-12和CVID3是一種跨膜蛋白，在人體中由基因CD19編碼^[5]^[6]，該蛋白存在於人體中所有B譜系細胞的表面^[7]^[8]，包含漿細胞確實表達CD19。^[9]^[10] CD19在人類B細胞中起著兩個主要作用：一方面，它可以做為信號轉導接頭蛋白，接收細胞質內的訊息傳遞分子；另一方面，它在CD19/CD21（英语：CD21）複合體內工作，降低B細胞受體信號通路的閾值。由於其在所有B細胞上的存在，它是B淋巴細胞發育、淋巴瘤診斷的生物標記，並且可以作為白血病免疫治療的靶點^[8]。

結構

在人類體內，CD19蛋白轉譯自「CD19」基因。該基因位於第16號染色體短臂上，長約7.41kb^[11]^[12]。該基因包含至少15個外顯子，其中4個外顯子轉譯為該蛋白的胞外結構（英语：extracellular domain），9個外顯子轉譯為細胞質結構，總共包含556個氨基酸^[12]。實驗顯示存在多種mRNA轉錄物，但只有其中兩個在體內發現^[11]。

CD19是一種95 kDa 免疫球蛋白超家族中的I型跨膜糖蛋白（IgSF（英语：Immunoglobulin superfamily）），具有兩個細胞外C2型Ig樣結構域（英语：C2-set Ig-like domain），和一條存在於細胞質部分的多肽尾端。該肽鏈由240個氨基酸所構成，相對胞外結構域較大，在哺乳動物物種演化中高度保守^[11]^[13]^[14]。細胞外C2型Ig樣結構域由一個潛在的二硫鍵非Ig樣結構域和N-鏈糖基化位點分隔。^[14]^[15] 細胞質尾部含有至少9個酪氨酸殘基，接近C端^[11]^[14] 在這些殘基中，Y391、Y482和Y513對CD19的生物功能至關重要。^[16]。Y482和Y513位點的苯丙氨酸替代導致其他酪氨酸的磷酸化受阻^[11]^[17]。

表達

CD19存在於自原始B細胞（Progenitor B cell）後期以後的各階段，包括漿細胞。當造血幹細胞開始往在B細胞譜系開始發育時，其免疫球蛋白（Ig）基因會開始進行基因重組，同時細胞表面開始出現CD19的表面標記^[8]。在發育過程中，CD19的表面密度受到高度調控^[11]，成熟B細胞的CD19表達量會增加為未成熟B細胞的三倍^[11]，但到發育為將細胞後又會逐漸下降^[18]。B細胞譜系的惡性腫瘤也會有CD19的表達^[7]^[17]，也因為CD19廣泛存在於大多數的B細胞，因此可以作為B細胞的表面標記，也是B細胞惡性腫瘤的治療標靶^[8]^[11]。

参考文献

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000177455 - Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 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.
^ Entrez Gene: CD19 CD19 molecule.
^ Tedder TF, Isaacs CM. Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes. A new member of the immunoglobulin superfamily. Journal of Immunology. July 1989, 143 (2): 712–717. PMID 2472450. S2CID 22081793. doi:10.4049/jimmunol.143.2.712.
^ ^7.0 ^7.1 Schroeder HW, Rich RR. Chapter 4: Antigen receptor genes, gene products, and co-receptors. Clinical immunology: Principles and Practice 4th. London: Elsevier Saunders. 2013: 47–51. ISBN 978-0-7234-3691-1. OCLC 823736017.
^ ^8.0 ^8.1 ^8.2 ^8.3 Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leukemia & Lymphoma. August 1995, 18 (5–6): 385–397. PMID 8528044. doi:10.3109/10428199509059636.
^ Merville P, Déchanet J, Desmoulière A, Durand I, de Bouteiller O, Garrone P, Banchereau J, Liu YJ. Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts. The Journal of Experimental Medicine. January 1996, 183 (1): 227–236. PMC 2192413  . PMID 8551226. doi:10.1084/jem.183.1.227.
^ Martín P, Santón A, Bellas C. Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis. Histopathology. April 2004, 44 (4): 375–380. PMID 15049904. S2CID 45937555. doi:10.1111/j.1365-2559.2004.01834.x.
^ ^11.0 ^11.1 ^11.2 ^11.3 ^11.4 ^11.5 ^11.6 ^11.7 Wang K, Wei G, Liu D. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Experimental Hematology & Oncology. November 2012, 1 (1): 36. PMC 3520838  . PMID 23210908. doi:10.1186/2162-3619-1-36  .
^ ^12.0 ^12.1 Zhou LJ, Ord DC, Omori SA, Tedder TF. Structure of the genes encoding the CD19 antigen of human and mouse B lymphocytes. Immunogenetics. 1992, 35 (2): 102–111. PMID 1370948. S2CID 7182703. doi:10.1007/bf00189519.
^ Mei HE, Schmidt S, Dörner T. Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity. Arthritis Research & Therapy. November 2012,. 14 Suppl 5 (Suppl 5): S1. PMC 3535716  . PMID 23281743. doi:10.1186/ar3909  .
^ ^14.0 ^14.1 ^14.2 Haas KM, Tedder TF. Role of the CD19 and CD21/35 Receptor Complex in Innate Immunity, Host Defense and Autoimmunity. Mechanisms of Lymphocyte Activation and Immune Regulation X. Advances in Experimental Medicine and Biology 560. Boston, MA: Springer. 2005: 125–139. ISBN 978-0-387-24188-3. PMID 15934172. doi:10.1007/0-387-24180-9_16.
^ Tedder TF. CD19: a promising B cell target for rheumatoid arthritis. Nature Reviews. Rheumatology. October 2009, 5 (10): 572–577. PMID 19798033. S2CID 6143992. doi:10.1038/nrrheum.2009.184.
^ Del Nagro CJ, Otero DC, Anzelon AN, Omori SA, Kolla RV, Rickert RC. CD19 function in central and peripheral B-cell development. Immunologic Research. 2005, 31 (2): 119–131. PMID 15778510. S2CID 45145420. doi:10.1385/IR:31:2:119.
^ ^17.0 ^17.1 Carter RH, Wang Y, Brooks S. Role of CD19 signal transduction in B cell biology. Immunologic Research. 2002, 26 (1–3): 45–54. PMID 12403344. S2CID 35818699. doi:10.1385/IR:26:1-3:045.
^ Fusconi, Massimo; Gallo, Andrea; De Virgilio, Armando; Natalizi, Stefania; Greco, Antonio; Zambetti, Giampietro; de Vincentiis, Marco. B Lymphocyte Subsets in Patients with Rhinoscleroma. Otolaryngology–Head and Neck Surgery. 2011-05, 144 (5). ISSN 0194-5998. doi:10.1177/0194599810396134 （英语）.

外部链接

Mouse CD Antigen Chart （页面存档备份，存于互联网档案馆）
Human CD Antigen Chart （页面存档备份，存于互联网档案馆）
Human CD19 genome location and CD19 gene details page in the UCSC Genome Browser（英语：UCSC Genome Browser）.

延伸閱讀

Goldsby, Richard A.; Kindt, Thomas J.; Osborne, Barbara A. Kuby Immunology. San Francisco: W. H. Freeman. 2006. ISBN 978-0-7167-8590-3.
Ishikawa H, Tsuyama N, Mahmoud MS, Fujii R, Abroun S, Liu S, Li FJ, Kawano MM. CD19 expression and growth inhibition of tumours in human multiple myeloma. Leukemia & Lymphoma. March 2002, 43 (3): 613–616. PMID 12002767. S2CID 20765908. doi:10.1080/10428190290012146.
Zhou LJ, Ord DC, Omori SA, Tedder TF. Structure of the genes encoding the CD19 antigen of human and mouse B lymphocytes. Immunogenetics. 1992, 35 (2): 102–111. PMID 1370948. S2CID 7182703. doi:10.1007/BF00189519.
Carter RH, Fearon DT. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science. April 1992, 256 (5053): 105–107. Bibcode:1992Sci...256..105C. PMID 1373518. doi:10.1126/science.1373518.
Kozmik Z, Wang S, Dörfler P, Adams B, Busslinger M. The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP. Molecular and Cellular Biology. June 1992, 12 (6): 2662–2672. PMC 364460  . PMID 1375324. doi:10.1128/mcb.12.6.2662.
Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF. The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. Journal of Immunology. November 1992, 149 (9): 2841–2850. PMID 1383329. S2CID 23655762. doi:10.4049/jimmunol.149.9.2841  .
Matsumoto AK, Kopicky-Burd J, Carter RH, Tuveson DA, Tedder TF, Fearon DT. 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. January 1991, 173 (1): 55–64. PMC 2118751  . PMID 1702139. doi:10.1084/jem.173.1.55.
Zhou LJ, Ord DC, Hughes AL, Tedder TF. 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. August 1991, 147 (4): 1424–1432. PMID 1714482. S2CID 1167309. doi:10.4049/jimmunol.147.4.1424  .
Stamenkovic I, Seed B. 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. September 1988, 168 (3): 1205–1210. PMC 2189043  . PMID 2459292. doi:10.1084/jem.168.3.1205.
Ord DC, Edelhoff S, Dushkin H, Zhou LJ, Beier DR, Disteche C, Tedder TF. CD19 maps to a region of conservation between human chromosome 16 and mouse chromosome 7. Immunogenetics. 1994, 39 (5): 322–328. PMID 7513297. S2CID 9336224. doi:10.1007/BF00189228.
Weng WK, Jarvis L, LeBien TW. 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. December 1994, 269 (51): 32514–32521. PMID 7528218. doi:10.1016/S0021-9258(18)31664-8  .
Myers DE, Jun X, Waddick KG, Forsyth C, Chelstrom LM, Gunther RL, Tumer NE, Bolen J, Uckun FM. 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. October 1995, 92 (21): 9575–9579. Bibcode:1995PNAS...92.9575M. PMC 40844  . PMID 7568175. doi:10.1073/pnas.92.21.9575  .
Chalupny NJ, Aruffo A, Esselstyn JM, Chan PY, Bajorath J, Blake J, Gilliland LK, Ledbetter JA, Tepper MA. 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. October 1995, 25 (10): 2978–2984. PMID 7589101. S2CID 9310907. doi:10.1002/eji.1830251040.
Tuscano JM, Engel P, Tedder TF, Agarwal A, Kehrl JH. 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. June 1996, 26 (6): 1246–1252. PMID 8647200. S2CID 29471624. doi:10.1002/eji.1830260610.
Carter RH, Doody GM, Bolen JB, Fearon DT. 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. April 1997, 158 (7): 3062–3069. PMID 9120258. S2CID 20717278. doi:10.4049/jimmunol.158.7.3062  .
Husson H, Mograbi B, Schmid-Antomarchi H, Fischer S, Rossi B. CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2. Oncogene. May 1997, 14 (19): 2331–2338. PMID 9178909. S2CID 967748. doi:10.1038/sj.onc.1201074.
Khine AA, Firtel M, Lingwood CA. 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. August 1998, 176 (2): 281–292. PMID 9648915. S2CID 10051140. doi:10.1002/(sici)1097-4652(199808)176:2<281::aid-jcp6>3.0.co;2-k.
Thunberg U, Gidlöf C, Bånghagen M, Sällström JF, Sundström C, Tötterman T. HpaII polymerase chain reaction restriction fragment length polymorphism in the human CD19 gene on 16p11. Human Heredity. 1998, 48 (4): 230–231. PMID 9694255. S2CID 32699676. doi:10.1159/000022806.
Horváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E. CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82. The Journal of Biological Chemistry. November 1998, 273 (46): 30537–30543. PMID 9804823. doi:10.1074/jbc.273.46.30537  .
Buhl AM, Cambier JC. 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. April 1999, 162 (8): 4438–4446. PMID 10201980. S2CID 23542951. doi:10.4049/jimmunol.162.8.4438  .

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000177455 - Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000030724 - Ensembl, May 2017

[3] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] Entrez Gene: CD19 CD19 molecule.

[pmid2472450-6] Tedder TF, Isaacs CM. Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes. A new member of the immunoglobulin superfamily. Journal of Immunology. July 1989, 143 (2): 712–717. PMID 2472450. S2CID 22081793. doi:10.4049/jimmunol.143.2.712.

[Schroeder_2013-7] 7.0 ^7.1 Schroeder HW, Rich RR. Chapter 4: Antigen receptor genes, gene products, and co-receptors. Clinical immunology: Principles and Practice 4th. London: Elsevier Saunders. 2013: 47–51. ISBN 978-0-7234-3691-1. OCLC 823736017.

[Scheuermann_1995-8] 8.0 ^8.1 ^8.2 ^8.3 Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leukemia & Lymphoma. August 1995, 18 (5–6): 385–397. PMID 8528044. doi:10.3109/10428199509059636.

[9] Merville P, Déchanet J, Desmoulière A, Durand I, de Bouteiller O, Garrone P, Banchereau J, Liu YJ. Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts. The Journal of Experimental Medicine. January 1996, 183 (1): 227–236. PMC 2192413  . PMID 8551226. doi:10.1084/jem.183.1.227.

[10] Martín P, Santón A, Bellas C. Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis. Histopathology. April 2004, 44 (4): 375–380. PMID 15049904. S2CID 45937555. doi:10.1111/j.1365-2559.2004.01834.x.

[Wang_2012-11] 11.0 ^11.1 ^11.2 ^11.3 ^11.4 ^11.5 ^11.6 ^11.7 Wang K, Wei G, Liu D. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Experimental Hematology & Oncology. November 2012, 1 (1): 36. PMC 3520838  . PMID 23210908. doi:10.1186/2162-3619-1-36  .

[Zhou_1992-12] 12.0 ^12.1 Zhou LJ, Ord DC, Omori SA, Tedder TF. Structure of the genes encoding the CD19 antigen of human and mouse B lymphocytes. Immunogenetics. 1992, 35 (2): 102–111. PMID 1370948. S2CID 7182703. doi:10.1007/bf00189519.

[Mei_2012-13] Mei HE, Schmidt S, Dörner T. Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity. Arthritis Research & Therapy. November 2012,. 14 Suppl 5 (Suppl 5): S1. PMC 3535716  . PMID 23281743. doi:10.1186/ar3909  .

[Haas_2005-14] 14.0 ^14.1 ^14.2 Haas KM, Tedder TF. Role of the CD19 and CD21/35 Receptor Complex in Innate Immunity, Host Defense and Autoimmunity. Mechanisms of Lymphocyte Activation and Immune Regulation X. Advances in Experimental Medicine and Biology 560. Boston, MA: Springer. 2005: 125–139. ISBN 978-0-387-24188-3. PMID 15934172. doi:10.1007/0-387-24180-9_16.

[Tedder_2009-15] Tedder TF. CD19: a promising B cell target for rheumatoid arthritis. Nature Reviews. Rheumatology. October 2009, 5 (10): 572–577. PMID 19798033. S2CID 6143992. doi:10.1038/nrrheum.2009.184.

[Del_Nagro_2005-16] Del Nagro CJ, Otero DC, Anzelon AN, Omori SA, Kolla RV, Rickert RC. CD19 function in central and peripheral B-cell development. Immunologic Research. 2005, 31 (2): 119–131. PMID 15778510. S2CID 45145420. doi:10.1385/IR:31:2:119.

[Carter_2002-17] 17.0 ^17.1 Carter RH, Wang Y, Brooks S. Role of CD19 signal transduction in B cell biology. Immunologic Research. 2002, 26 (1–3): 45–54. PMID 12403344. S2CID 35818699. doi:10.1385/IR:26:1-3:045.

[18] Fusconi, Massimo; Gallo, Andrea; De Virgilio, Armando; Natalizi, Stefania; Greco, Antonio; Zambetti, Giampietro; de Vincentiis, Marco. B Lymphocyte Subsets in Patients with Rhinoscleroma. Otolaryngology–Head and Neck Surgery. 2011-05, 144 (5). ISSN 0194-5998. doi:10.1177/0194599810396134 （英语）.

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