Benedict C L, Gilfillan S, Thai T H, Kearney J F
Princeton University, Department of Molecular Biology, New Jersey, USA.
Immunol Rev. 2000 Jun;175:150-7.
In mice, the absence of terminal deoxynucleotidyl transferase (Tdt) expression during fetal and neonatal life provides a window in development where clones of lymphocytes are generated that provide protective immunity. Introducing premature Tdt activity interferes with the development of these clones and results in an impaired ability to make protective antibodies. Conversely, gene-targeted disruption of Tdt prevents N additions at all stages of T and B-lymphocyte development and promotes the development of fetal-like T and B-cell clones into adulthood, with accompanying alterations in repertoire. The alternative splice forms of Tdt may be necessary to provide regulatory mechanisms to restrict N addition to appropriate stages of the developmental pathways, the details of which are being revealed. The evidence continues to build that Tdt is a key player in influencing the outcome of V(D)J recombination during lymphocyte and repertoire development.
在小鼠中，胎儿期和新生儿期缺乏末端脱氧核苷酸转移酶（Tdt）表达，为淋巴细胞克隆的产生提供了一个发育窗口，这些克隆可提供保护性免疫。引入过早的Tdt活性会干扰这些克隆的发育，并导致产生保护性抗体的能力受损。相反，Tdt的基因靶向破坏会阻止T和B淋巴细胞发育的所有阶段发生N添加，并促进胎儿样T和B细胞克隆发育至成年期，同时伴随着谱系的改变。Tdt的可变剪接形式可能是提供调控机制以将N添加限制在发育途径的适当阶段所必需的，其细节正在被揭示。越来越多的证据表明，Tdt是影响淋巴细胞和谱系发育过程中V(D)J重组结果的关键因素。
