Dörner T, Foster S J, Farner N L, Lipsky P E
Department of Internal Medicine and Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235, USA.
J Clin Invest. 1998 Aug 15;102(4):688-94. doi: 10.1172/JCI3113.
To determine whether receptor editing of Vkappa genes was involved in the pathogenesis of systemic lupus erythematosus (SLE), the usage of Vkappa and Jkappa gene elements from individual peripheral CD19(+) B cells obtained from a patient with untreated SLE was examined. No differences in the Vkappa and Jkappa gene usage in the nonproductive gene repertoire of this SLE patient were noted compared with the distribution of genes found in normal adults. However, an increased usage of Jkappa5 segments, and a significant overrepresentation of the Vkappa1 and Vkappa4 families, especially the L15, O14/O4, and B3 genes characterized the productive Vkappa gene repertoire of the SLE patient. Furthermore, Jkappa5-containing Vkappa gene rearrangements in the productive but not the nonproductive repertoire manifested significantly fewer mutations compared with Vkappa genes recombined with Jkappa1-4. These data are consistent with the conclusion that receptor editing of Vkappa is much more apparent in this SLE patient than in normals and suggest that a deficiency in this means to counteract the emergence of autoimmunity is not an essential feature of SLE.
为了确定Vκ基因的受体编辑是否参与系统性红斑狼疮（SLE）的发病机制，对一名未经治疗的SLE患者外周血单个CD19(+) B细胞中Vκ和Jκ基因元件的使用情况进行了检测。与正常成年人中发现的基因分布相比，该SLE患者非功能性基因库中Vκ和Jκ基因的使用情况没有差异。然而，Jκ5片段的使用增加，以及Vκ1和Vκ4家族的显著过度表达，尤其是L15、O14/O4和B3基因，是该SLE患者功能性Vκ基因库的特征。此外，与与Jκ1-4重组的Vκ基因相比，在功能性而非非功能性基因库中含Jκ5的Vκ基因重排表现出明显更少的突变。这些数据与以下结论一致，即该SLE患者中Vκ的受体编辑比正常人更明显，并表明这种对抗自身免疫出现的手段的缺陷不是SLE的本质特征。
