Xu Yuekang, Fairfax Kirsten, Light Amanda, Huntington Nicholas D, Tarlinton David M
The Walter and Eliza Hall Institute of Medical Research , Department of Medical Biology, The University of Melbourne , Australia .
Autoimmunity. 2014 Nov;47(7):430-7. doi: 10.3109/08916934.2014.921810. Epub 2014 Jun 23.
CD19 is a co-stimulatory surface protein expressed exclusively on B cells and serves to reduce the threshold for signalling via the B-cell receptor (BCR). Co-ligation of CD19 with the BCR synergistically enhances mitogen-activated protein (MAP) kinase activity, calcium release and proliferation. We recently found that these parameters were also enhanced in CD19-null primary murine B cells following BCR ligation, suggesting a regulatory role for CD19 in BCR signalling. In this study, we demonstrate that the enhanced BCR signalling in the absence of CD19 was not dependent on the src kinase Lyn, but linked to phosphoinositide 3-kinase (PI3K) activity. Consistent with this, we detect PI3K associated with CD19 outside the lipid raft in resting B cells. Pre-ligation of CD19 to restrict its translocation with the BCR into lipid rafts attenuated BCR-induced PI3K and MAP kinase activation and subsequent B-cell proliferation. Thus, we propose that CD19 can modulate BCR signalling in both a positive and negative manner depending on the receptor/ligand interaction in vivo.
CD19是一种共刺激表面蛋白，仅在B细胞上表达，其作用是降低通过B细胞受体（BCR）进行信号传导的阈值。CD19与BCR的共连接可协同增强丝裂原活化蛋白（MAP）激酶活性、钙释放和细胞增殖。我们最近发现，在BCR连接后，这些参数在CD19基因敲除的原代小鼠B细胞中也有所增强，这表明CD19在BCR信号传导中具有调节作用。在本研究中，我们证明在没有CD19的情况下增强的BCR信号传导不依赖于src激酶Lyn，而是与磷脂酰肌醇3激酶（PI3K）活性有关。与此一致的是，我们在静息B细胞的脂筏外检测到与CD19相关的PI3K。预先连接CD19以限制其与BCR一起转运到脂筏中，可减弱BCR诱导的PI3K和MAP激酶活化以及随后的B细胞增殖。因此，我们提出，CD19可以根据体内受体/配体的相互作用以正向和负向方式调节BCR信号传导。
