Genetic analysis of the variable region genes encoding a monospecific human natural anti-DNA antibody.
Genetic analysis of the variable region genes encoding a monospecific human natural anti-DNA antibody.
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编码单特异性人类天然抗 DNA 抗体的可变区基因的遗传分析。
DOI：
10.1111/j.1365-2249.1993.tb06490.x
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发表时间：
1993
影响因子：
4.6
通讯作者：
Siminovitch,KA
中科院分区：
文献类型：
--
作者：
Daley,MD;Misener,V;Olee,T;Chen,PP;Siminovitch,KA
最近的证据表明，天然的自身抗体可能在正常免疫库的发展中发挥不可或缺的作用。为了探索这些抗体的遗传起源，我们分离并测序了编码天然抗DNA抗体Kim It的重链（H）和轻链（L）的可变（V）区基因。这些基因似乎来源于VH4.t8（亚组VHIV）、JH5、JIILI（亚组VλI）和Jλ3生殖系基因。H链多样性基因的起源更模糊，可能来自几个种系基因中的一个或多个，以正向或反向方向排列。Kim 11.4 VHand VL基因与其它自身抗体中使用的基因具有显著程度的相似性，表明在人自身反应性B细胞中可能存在至少某种程度的V限制。Kim 11.4 VHand VL基因与其假定的种系对应物之间的核苷酸差异的模式表明Kim 11.4基因可能经历了体细胞突变并作为抗原选择的结果而出现。
Recent evidence suggests that natural autoantibodies may play an integral rote in the development of the normal immune repertoire. To explore the genetic origins of these antibodies, we have isolated and sequenced the variable (V) region genes encoding both the heavy (H) and light (L) chains of a natural anti‐DNA antibody, Kim It.4. The genes appear to be derived from the VH4.t8 (subgroup VHIV), JH5, Hum ILI (subgroup VλI) and Jλ3 germline genes. The origin of the H chain diversity gene is more obscure, being potentially derived from one or more of several germline genes, arranged in either the forward or reverse orientations. Both the Kim 11.4 VHand VLgenes share significant degrees of similarity with those utilized in other autoantibodies, indicating that at least some degree of V restriction may exist in human autoreactive B cells. The pattern of nucleotide differences between the Kim 11.4 VHand VLgenes and their putative germline counterparts suggests that the Kim 11.4 genes may have undergone somatic mutation and arisen as a result of antigen selection.