Wallace V A, Fung-Leung W P, Timms E, Gray D, Kishihara K, Loh D Y, Penninger J, Mak T W
Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, Canada.
J Exp Med. 1992 Dec 1;176(6):1657-63. doi: 10.1084/jem.176.6.1657.
CD45 is a protein tyrosine phosphatase involved in T and B cell signaling. While peripheral T cells switch CD45 isoforms upon activation, events leading to exon switching during T cell development in the thymus have not been determined. The expression of high molecular weight isoforms of CD45 was examined on thymocytes from nontransgenic and T cell receptor (TCR) transgenic mice. All thymocytes from nontransgenic mice were CD45RB+ as assessed by staining with MB23G2, an anti-CD45RB-specific monoclonal antibody. Interestingly, there was a small population (1-3%) of thymocytes that displayed a higher intensity of staining with MB23G2, CD45RBhigh. CD45RBhigh thymocytes were found in all subsets defined by CD4 and CD8 expression and were also present within the TCR-alpha/beta high population. To analyze whether or not CD45 expression correlated with thymic selection events, expression of CD45RBhigh and a second isoform, CD45RA, was examined on thymocytes from H-Y and 2C TCR transgenic mice and found to correlate with positive and negative selection events but did not occur in nonselecting backgrounds. CD45RA and CD45RBhigh upregulation was also not observed in transgenic mice backcrossed into CD8-deficient mice, a scenario in which there is no positive selection of transgene-expressing thymocytes. These data suggest that modulation of CD45 isoform expression may be involved in thymic selection events.
CD45是一种参与T细胞和B细胞信号传导的蛋白酪氨酸磷酸酶。虽然外周T细胞在激活时会切换CD45异构体，但导致胸腺中T细胞发育过程中外显子切换的事件尚未确定。对非转基因和T细胞受体（TCR）转基因小鼠的胸腺细胞进行了高分子量CD45异构体表达的检测。用抗CD45RB特异性单克隆抗体MB23G2染色评估，非转基因小鼠的所有胸腺细胞均为CD45RB+。有趣的是，有一小部分（1 - 3%）胸腺细胞用MB23G2染色时显示出更高的强度，即CD45RB高表达。在由CD4和CD8表达定义的所有亚群中都发现了CD45RB高表达的胸腺细胞，并且在TCR-α/β高表达群体中也存在。为了分析CD45表达是否与胸腺选择事件相关，检测了H-Y和2C TCR转基因小鼠胸腺细胞上CD45RB高表达和第二种异构体CD45RA的表达，发现其与阳性和阴性选择事件相关，但在非选择背景中不发生。在回交到CD8缺陷小鼠的转基因小鼠中也未观察到CD45RA和CD45RB高表达上调，在这种情况下，表达转基因的胸腺细胞没有阳性选择。这些数据表明，CD45异构体表达的调节可能参与胸腺选择事件。
