Bentolila L A, Olson S, Marshall A, Rougeon F, Paige C J, Doyen N, Wu G E
Unité de Génétique et Biochimie du Développement, Unité de Recherche Associée, Centre National de la Recherche Scientifique 1960, Département d'Immunologie, Institut Pasteur, Paris, France.
J Immunol. 1999 Feb 15;162(4):2123-8.
Nontemplated (N) nucleotide additions contribute significantly to the junctional diversity of all Ag receptor chains in adult mice except Ig light (L) chains, primarily because terminal deoxynucleotidyl transferase (TdT) expression is turned off at the time of their rearrangement in pre-B cells. However, because some Ig L chain gene rearrangements are detectable earlier during B cell ontogeny when TdT expression is thought to be maximal, we have examined the junctional processing of kappa- and lambda-chain genes of CD45(B220)+CD43+ pro-B cells from mu MT mice. We found that both kappa and lambda coding junctions formed in these B cell precursors were extensively diversified with N-region additions. Together, these findings demonstrate that Ig L chain genes are equally accessible to TdT in pro-B cells as Ig heavy chain genes. Surprisingly, however, the two L chain isotypes differed in the pattern of N addition, which was more prevalent at the lambda-chain locus. We observed the same diversity pattern in pre-B cells from TdT-transgenic mice. These results suggest that some aspects of TdT processing could be influenced by factors intrinsic to the sequence of Ig genes and/or the process of V(D)J recombination itself.
非模板化（N）核苷酸添加对成年小鼠中除免疫球蛋白轻链（L链）外的所有抗原受体链的连接多样性有显著贡献，主要原因是末端脱氧核苷酸转移酶（TdT）在pre-B细胞中重排时表达关闭。然而，由于在B细胞发生过程中，当TdT表达被认为达到最大值时，一些免疫球蛋白L链基因重排更早可被检测到，我们检测了来自μMT小鼠的CD45（B220）+CD43+前B细胞的κ链和λ链基因的连接加工情况。我们发现，在这些B细胞前体中形成的κ链和λ链编码连接都通过N区添加而广泛多样化。这些发现共同表明，在pro-B细胞中，免疫球蛋白L链基因与免疫球蛋白重链基因一样，都能被TdT作用。然而，令人惊讶的是，两种L链同种型在N添加模式上存在差异，这种差异在λ链基因座更为普遍。我们在TdT转基因小鼠的pre-B细胞中观察到相同的多样性模式。这些结果表明，TdT加工的某些方面可能受免疫球蛋白基因序列内在因素和/或V（D）J重组过程本身的影响。
