Klein R, Jaenichen R, Zachau H G
Institut für Physiologische Chemie, Universität München, Germany.
Eur J Immunol. 1993 Dec;23(12):3248-62. doi: 10.1002/eji.1830231231.
The question of which germ-line V kappa genes are expressed was studied by sequencing 70 different cDNA clones from a human spleen library and one clone from a fetal liver library. The sequences were compared to a data base containing all germ-line V kappa gene and pseudogene sequences. In addition, 51 rearranged genomic V kappa genes, 170 cDNA and 74 kappa proteins from the literature were assigned to specific germ-line V kappa genes and included in the comparisons. Not all the known, potentially functional V kappa genes were found to be expressed, while some genes with minor defects are. The total number of expressed genes is smaller than expected: so far 21 germ-line genes and 5 pairs of duplicated identical genes are known to be transcribed. The corresponding numbers for rearranged genomic V kappa genes and kappa proteins are 17 plus 4 and 7 plus 7, respectively. A second aim of the study was to find out whether the expressed repertoire contains derivatives of germ-line V kappa genes still missing in our data base; no evidence for the existence of such genes was found. Several cDNA clones contained additional nucleotides between the V kappa and J kappa gene segments, which may be germ-line derived, inserted by terminal deoxynucleotidyl transferase or introduced by other mechanisms. Somatic gene conversion seems not to play a major role in creating the human kappa gene diversity. Various aspects of the hypermutation of kappa genes are discussed and the formation of block mutations, i.e. the alterations of two or more adjacent nucleotides is stressed as a remarkable feature of the process.
通过对来自人脾脏文库的70个不同cDNA克隆和来自胎儿肝脏文库的1个克隆进行测序，研究了哪些种系Vκ基因被表达。将这些序列与包含所有种系Vκ基因和假基因序列的数据库进行比较。此外，还将文献中的51个重排的基因组Vκ基因、170个cDNA和74个κ蛋白指定到特定的种系Vκ基因，并纳入比较。并非所有已知的、具有潜在功能的Vκ基因都被发现有表达，而一些有轻微缺陷的基因却有表达。表达基因的总数比预期的要少：到目前为止，已知有21个种系基因和5对重复的相同基因被转录。重排的基因组Vκ基因和κ蛋白的相应数字分别为17加4和7加7。该研究的第二个目的是查明表达的基因库中是否包含我们数据库中仍缺失的种系Vκ基因的衍生物；未发现存在此类基因的证据。几个cDNA克隆在Vκ和Jκ基因片段之间含有额外的核苷酸，这些核苷酸可能是种系衍生的，由末端脱氧核苷酸转移酶插入或通过其他机制引入。体细胞基因转换似乎在产生人类κ基因多样性方面不起主要作用。讨论了κ基因超突变的各个方面，并强调了块突变的形成，即两个或更多相邻核苷酸的改变是该过程的一个显著特征。
