Division of Hematology and Oncology, Department of Medicine, New York Medical College and Westchester Medical Center, Valhalla, NY 10595, USA.
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Exp Hematol Oncol. 2012 Nov 29;1(1):36. doi: 10.1186/2162-3619-1-36.
The human CD19 antigen is a 95 kd transmembrane glycoprotein belonging to the immunoglobulin superfamily. CD19 is classified as a type I transmembrane protein, with a single transmembrane domain, a cytoplasmic C-terminus, and extracellular N-terminus. CD19 is a biomarker for normal and neoplastic B cells, as well as follicular dendritic cells. CD19 is critically involved in establishing intrinsic B cell signaling thresholds through modulating both B cell receptor-dependent and independent signaling. CD19 functions as the dominant signaling component of a multimolecular complex on the surface of mature B cells, alongside complement receptor CD21, and the tetraspanin membrane protein CD81 (TAPA-1), as well as CD225. Through study of CD19 transgenic and knockout mouse models, it becomes clear that CD19 plays a critical role in maintaining the balance between humoral, antigen-induced response and tolerance induction. This review also summarized latest clinical development of CD19 antibodies, anti-B4-bR (an immunotoxin conjugate), blinatumomab (BiTE), and SAR3419 (huB4-DM4), a novel antibody-drug conjugate.
人 CD19 抗原是一种 95 kd 的跨膜糖蛋白,属于免疫球蛋白超家族。CD19 被归类为 I 型跨膜蛋白,具有单一的跨膜结构域、胞质 C 末端和细胞外 N 末端。CD19 是正常和肿瘤 B 细胞以及滤泡树突状细胞的标志物。CD19 通过调节 B 细胞受体依赖性和非依赖性信号传导,在建立内在 B 细胞信号转导阈值方面起着至关重要的作用。CD19 作为成熟 B 细胞表面多分子复合物的主要信号成分,与补体受体 CD21 和四跨膜蛋白 CD81(TAPA-1)以及 CD225 一起发挥作用。通过对 CD19 转基因和敲除小鼠模型的研究,清楚地表明 CD19 在维持体液、抗原诱导的反应和诱导耐受之间的平衡中起着关键作用。本文还总结了 CD19 抗体、抗 B4-bR(免疫毒素偶联物)、blinatumomab(BiTE)和 SAR3419(huB4-DM4,一种新型抗体药物偶联物)的最新临床进展。