Komori T, Pricop L, Hatakeyama A, Bona C A, Alt F W
Department of Medicine III, Osaka University Medical School, Japan.
Int Rev Immunol. 1996;13(4):317-25. doi: 10.3109/08830189609061755.
Tdt deficient mice show lack of N region in V(D)J junctions of immunoglobulin and T cell receptor genes and revealed that "immature recombinase" in fetal stage would boil down to no more than a lack of Tdt. Although particular junctions which are thought to be created by homology-mediated joining are frequently observed, one fourth of junctions lacked even one bp of overlap, indicating the existence of a V(D)J joining pathway that is homology independent. Lymphocyte repertoire which express VH81X gene without N region is negatively selected, which shows that the repertoire of Tdt deficient mice is not a truly fetal repertoire. Positive selection of thymocytes is more efficient in Tdt deficient mice. Furthermore Tdt-/- mice produce significant amounts of anti-dsDNA antibodies as Tdt+/+ mice, indicating that increased diversity of the third complementarity-determining region (CDR3) by Tdt is not essential for the expansion of precursor B cells programmed to produce anti-DNA antibodies.
末端脱氧核苷酸转移酶(Tdt)缺陷小鼠在免疫球蛋白和T细胞受体基因的V(D)J连接中显示缺乏N区,并表明胎儿期的“未成熟重组酶”归根结底只不过是缺乏Tdt。尽管经常观察到被认为是由同源性介导的连接产生的特定连接,但四分之一的连接甚至缺乏一个碱基对的重叠,这表明存在一条不依赖同源性的V(D)J连接途径。不表达带有N区的VH81X基因的淋巴细胞谱系被阴性选择,这表明Tdt缺陷小鼠的谱系不是真正的胎儿谱系。Tdt缺陷小鼠中胸腺细胞的阳性选择更有效。此外,Tdt-/-小鼠与Tdt+/+小鼠一样产生大量抗双链DNA抗体,这表明Tdt增加的第三个互补决定区(CDR3)的多样性对于编程产生抗DNA抗体的前体B细胞的扩增并非必不可少。