Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice
Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice
复制标题
DOI：
10.1016/s1074-7613(00)80060-6
复制
发表时间：
1999-05-01
期刊：
影响因子：
32.4
通讯作者：
Kearney, JF
中科院分区：
文献类型：
--
作者：
Benedict, CL;Kearney, JF
胎儿免疫球蛋白的多样性低于成人免疫球蛋白，这主要是因为在没有Tdt的情况下缺乏N添加。为了测试Tdt的缺失是否是必需的，我们产生了表达Tdt并在胎儿B细胞中添加N区的Tg小鼠。当成年小鼠被含PC的肺炎链球菌攻击时，这些小鼠不能产生由IG H和L链基因的典型重排编码的标志性T15抗PC Ab。来自这些小鼠的抗PC Ab被过早的N添加改变，并且不能防止致命的肺炎球菌感染引起的死亡。这些结果表明，维持较低的IG多样性在生命早期是必不可少的收购一个完整的功能性成人剧目。
Fetal Igs are less diverse than adult Igs, largely because of the lack of N addition in the absence of Tdt. To test whether the absence of Tdt is essential, we generated Tg mice that express Tdt and add N regions in fetal B cells. When challenged as adults with PC-containing Streptococcus pneumoniae, these mice fail to make the hallmark T15 anti-PC Ab encoded by canonical rearrangements of Ig H and L chain genes. The anti-PC Abs from these mice are altered by premature N addition and do not protect against death from virulent pneumococcal infection. These results show that maintenance of lower Ig diversity in early life is essential for the acquisition of a complete functional adult repertoire.