Uckun F M, Burkhardt A L, Jarvis L, Jun X, Stealey B, Dibirdik I, Myers D E, Tuel-Ahlgren L, Bolen J B
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Health Sciences Center, Minneapolis 55455.
J Biol Chem. 1993 Oct 5;268(28):21172-84.
We present evidence that the CD19 receptor is functionally operative and transmits pleiotropic signals throughout the pro-B, pre-pre-B, pre-B, early B, and mature B cell stages of human B-cell ontogeny. The signaling ability of CD19 does not depend on the existence of a functional B-cell antigen receptor complex (ARC). In B-cell precursors (BCP) lacking a functional ARC, CD19 is physically and functionally associated with Src family protein tyrosine kinases (PTK). The engagement of the CD19 receptor on BCP with a high affinity anti-CD19 monoclonal antibody (mAb) or its homoconjugate rapidly activates the associated PTK and results in tyrosine phosphorylation of CD19. Moreover, this proximal PTK activation step triggers downstream stimulation of several different intracellular messenger systems. Remarkably, CD19 becomes rapidly phosphorylated on tyrosine residues upon engagement of several other surface receptors as well, suggesting that it may function as a common response element linked via tyrosine phosphorylation to multiple BCP/B-cell receptors and signaling pathways. Furthermore, in all B-lineage lymphoid cell populations, co-approximation of the receptors CD19 and CD72 (ligand for the CD5 T-cell receptor) generates a stronger signal than the engagement of either individual receptor. These convergent observations constitute a strong argument for an important regulatory function of CD19 in human BCP and prompt the hypothesis that the CD19 receptor may play an important role in cognate interactions between B- and T-lineage lymphoid compartments as well as the coordinate production of BCP at multiple stages of human B-cell ontogeny.
我们提供的证据表明，CD19受体在功能上是可操作的，并且在人类B细胞发育的前B细胞、前前B细胞、前B细胞、早期B细胞和成熟B细胞阶段传递多效性信号。CD19的信号传导能力不依赖于功能性B细胞抗原受体复合物（ARC）的存在。在缺乏功能性ARC的B细胞前体（BCP）中，CD19在物理和功能上与Src家族蛋白酪氨酸激酶（PTK）相关联。用高亲和力抗CD19单克隆抗体（mAb）或其同型共轭物使BCP上的CD19受体结合，可迅速激活相关的PTK，并导致CD19的酪氨酸磷酸化。此外，这一近端PTK激活步骤会触发几种不同细胞内信使系统的下游刺激。值得注意的是，当其他几种表面受体结合时，CD19也会在酪氨酸残基上迅速磷酸化，这表明它可能作为一个共同的反应元件，通过酪氨酸磷酸化与多个BCP/B细胞受体和信号通路相连。此外，在所有B系淋巴细胞群体中，受体CD19和CD72（CD5 T细胞受体的配体）的共同接近产生的信号比单个受体结合时更强。这些一致的观察结果有力地证明了CD19在人类BCP中的重要调节功能，并促使人们提出这样的假设：CD19受体可能在B细胞和T细胞系淋巴细胞隔室之间的同源相互作用以及人类B细胞发育多个阶段BCP的协调产生中发挥重要作用。
