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CD19

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CD19
識別號
别名CD19;, B4, CVID3, CD19 molecule
外部IDOMIM107265 MGI88319 HomoloGene1341 GeneCardsCD19
基因位置(人类
16號染色體
染色体16號染色體[1]
16號染色體
CD19的基因位置
CD19的基因位置
基因座16p11.2起始28,931,965 bp[1]
终止28,939,342 bp[1]
RNA表达模式
查阅更多表达数据
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

NM_001178098
​NM_001770
​NM_001385732

NM_009844
​NM_001357091

蛋白序列

NP_001171569
​NP_001761

NP_033974
​NP_001344020

基因位置​(UCSC)Chr 16: 28.93 – 28.94 MbChr 7: 126.01 – 126.01 Mb
PubMed​查找[3][4]
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B4T細胞表面抗原Leu-12CVID3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

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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

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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

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  1. ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000177455 - Ensembl, May 2017
  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. 
  5. ^ Entrez Gene: CD19 CD19 molecule. 
  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. 
  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. 
  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可免费查阅. 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. 
  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可免费查阅. PMID 23210908. doi:10.1186/2162-3619-1-36可免费查阅. 
  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. 
  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可免费查阅. PMID 23281743. doi:10.1186/ar3909可免费查阅. 
  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. 
  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. 
  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. 
  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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