CD19

CD19
识别号
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号染色体
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
基因本体
分子功能	• 血浆蛋白结合; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity;
细胞组分	• integral component of membrane; • 细胞膜; • integral component of plasma membrane; • 外排体; • 膜; • external side of plasma membrane; • 大分子复合体; • 脂筏模型;
生物学过程	• 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
	维基数据
查看/编辑人类	查看/编辑小鼠

B淋巴细胞抗原CD19（B-lymphocyte antigen CD19），也称为CD19分子（Cluster of Differentiation 19），B淋巴细胞表面抗原B4、T细胞表面抗原Leu-12和CVID3是一种跨膜蛋白，在人体中由基因CD19编码^[5]^[6]，该蛋白存在于人体中所有B谱系细胞的表面^[7]^[8]，包含浆细胞确实表达CD19。^[9]^[10] CD19在人类B细胞中起著两个主要作用：一方面，它可以做为信号转导接头蛋白，接收细胞质内的信号转导分子；另一方面，它在CD19/CD21（英语：CD21）复合体内工作，降低B细胞受体信号通路的阈值。由于其在所有B细胞上的存在，它是B淋巴细胞发育、淋巴瘤诊断的生物标记，并且可以作为白血病免疫治疗的靶点^[8]。

结构

在人类体内，CD19蛋白翻译自“CD19”基因。该基因位于第16号染色体短臂上，长约7.41kb^[11]^[12]。该基因包含至少15个外显子，其中4个外显子翻译为该蛋白的胞外结构（英语：extracellular domain），9个外显子翻译为细胞质结构，总共包含556个氨基酸^[12]。实验显示存在多种mRNA转录物，但只有其中两个在体内发现^[11]。

CD19是一种95 kDa 免疫球蛋白超家族中的I型跨膜糖蛋白（IgSF（英语：Immunoglobulin superfamily）），具有两个细胞外C2型Ig样结构域（英语：C2-set Ig-like domain），和一条存在于细胞质部分的多肽尾端。该肽链由240个氨基酸所构成，相对胞外结构域较大，在哺乳动物物种演化中高度保守^[11]^[13]^[14]。细胞外C2型Ig样结构域由一个潜在的二硫键非Ig样结构域和N-链糖基化位点分隔。^[14]^[15] 细胞质尾部含有至少9个酪氨酸残基，接近C端^[11]^[14] 在这些残基中，Y391、Y482和Y513对CD19的生物功能至关重要。^[16]。Y482和Y513位点的苯丙氨酸替代导致其他酪氨酸的磷酸化受阻^[11]^[17]。

表达

CD19存在于自原始B细胞（Progenitor B cell）后期以后的各阶段，包括浆细胞。当造血干细胞开始往在B细胞谱系开始发育时，其免疫球蛋白（Ig）基因会开始进行基因重组，同时细胞表面开始出现CD19的表面标记^[8]。在发育过程中，CD19的表面密度受到高度调控^[11]，成熟B细胞的CD19表达量会增加为未成熟B细胞的三倍^[11]，但到发育为将细胞后又会逐渐下降^[18]。B细胞谱系的恶性肿瘤也会有CD19的表达^[7]^[17]，也因为CD19广泛存在于大多数的B细胞，因此可以作为B细胞的表面标记，也是B细胞恶性肿瘤的治疗标靶^[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）.

延伸阅读

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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