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CD19

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CD19
识别号
别名CD19;, B4, CVID3, CD19 molecule
外部IDOMIM107265 MGI88319 HomoloGene1341 GeneCardsCD19
基因位置(人类
16号染色体
染色体16号染色体[1]
16号染色体
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
物种人类小鼠
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]
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B4T细胞表面抗原Leu-12CVID3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

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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

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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

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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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