Generation of immunoglobulin light chain gene diversity in Raja erinacea is not associated with somatic rearrangement, an exception to a central paradigm of B cell immunity.
Generation of immunoglobulin light chain gene diversity in Raja erinacea is not associated with somatic rearrangement, an exception to a central paradigm of B cell immunity.
复制标题
DOI：
10.1084/jem.182.1.109
复制
发表时间：
1995-07-01
期刊：
影响因子：
--
通讯作者：
Litman GW
中科院分区：
文献类型：
--
作者：
Anderson MK;Shamblott MJ;Litman RT;Litman GW
在所有脊椎动物物种的检查日期，重排和体细胞修饰的基因节段性元件，编码免疫球蛋白的抗原结合位点的部分是抗体多样性的产生的组成部分。在遗传学上原始的软骨鱼类中，编码免疫球蛋白重链和轻链位点的基因片段排列成多个簇，其中片段元件仅相隔300-400 bp。在某些情况下，节段元件在非淋巴细胞的生殖细胞中连接（连接基因）。基因组文库筛选和基因组DNA的直接扩增已被用来表征至少89个不同的I型轻链基因簇的滑冰，拉贾。预测的核苷酸序列和预测的肽结构的分析与基因到不同序列组中的分布一致。预测的氨基酸序列差异优先分布在互补决定区与框架区，并且互补型取代超过中性取代。当特定的种系序列与单个cDNA的序列相关时，很明显，连接的基因被表达并且可能发生体细胞突变。没有证据表明拉贾中存在任何I型轻链基因，而不是种系连接。拉贾的I型轻链基因簇似乎代表了一种新的基因系统，其中组合和连接多样性是不存在的。
In all vertebrate species examined to date, rearrangement and somatic modification of gene segmental elements that encode portions of the antigen-combining sites of immunoglobulins are integral components of the generation of antibody diversity. In the phylogenetically primitive cartilaginous fishes, gene segments encoding immunoglobulin heavy and light chain loci are arranged in multiple clusters, in which segmental elements are separated by only 300-400 bp. In some cases, segmental elements are joined in the germline of nonlymphoid cells (joined genes). Both genomic library screening and direct amplification of genomic DNA have been used to characterize at least 89 different type I light chain gene clusters in the skate, Raja. Analyses of predicted nucleotide sequences and predicted peptide structures are consistent with the distribution of genes into different sequence groups. Predicted amino acid sequence differences are preferentially distributed in complementarity-determining versus framework regions, and replacement-type substitutions exceed neutral substitutions. When specific germline sequences are related to the sequences of individual cDNAs, it is apparent that the joined genes are expressed and are potentially somatically mutated. No evidence was found for the presence of any type I light chain gene in Raja that is not germline joined. The type I light chain gene clusters in Raja appear to represent a novel gene system in which combinatorial and junctional diversity are absent.