Wen Lijun, Brill-Dashoff Joni, Shinton Susan A, Asano Masanao, Hardy Richard R, Hayakawa Kyoko
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Immunity. 2005 Sep;23(3):297-308. doi: 10.1016/j.immuni.2005.08.007.
Antigen receptor-mediated signaling is critical for the development and survival of B cells. However, it has not been established whether B cell development requires a signal from self-ligand engagement at the immature stage, a process known as "positive selection." Here, using a monoclonal B cell receptor (BCR) mouse line, specific for the self-Thy-1/CD90 glycoprotein, we demonstrate that BCR crosslinking by low-dose self-antigen promotes survival of immature B cells in culture. In spleen, an increase in BCR signaling strength, induced by low-dose self-antigen, directed naive immature B cells to mature, not into the default follicular B cell fate, but instead into the marginal-zone B cell subset. These data indicate that positive selection can occur in developing B cells and that BCR signal strength is a key factor in deciding between two functionally distinct mature B cell compartments in the microenvironment of the spleen.
抗原受体介导的信号传导对于B细胞的发育和存活至关重要。然而,尚未确定B细胞发育在未成熟阶段是否需要来自自身配体结合的信号,这一过程称为“阳性选择”。在此,我们使用对自身Thy-1/CD90糖蛋白具有特异性的单克隆B细胞受体(BCR)小鼠品系,证明低剂量自身抗原引起的BCR交联可促进培养中未成熟B细胞的存活。在脾脏中,低剂量自身抗原诱导的BCR信号强度增加,引导幼稚未成熟B细胞成熟,不是进入默认的滤泡B细胞命运,而是进入边缘区B细胞亚群。这些数据表明,发育中的B细胞可发生阳性选择,并且BCR信号强度是在脾脏微环境中决定两个功能不同的成熟B细胞区室的关键因素。