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原发性干燥综合征(pSS)患者类风湿因子(RF)的轻链可变区(VL)序列:体细胞超突变的中度贡献

Light chain variable (VL) sequences of rheumatoid factors (RF) in patients with primary Sjögren's syndrome (pSS): moderate contribution of somatic hypermutation.

作者信息

Elagib K E, Børretzen M, Thompson K M, Natvig J B

机构信息

Institute of Nuclear Medicine and Molecular Biology, University of Gezira, Wad Medani, Sudan.

出版信息

Scand J Immunol. 1999 Nov;50(5):492-8. doi: 10.1046/j.1365-3083.1999.00624.x.

DOI:10.1046/j.1365-3083.1999.00624.x
PMID:10564552
Abstract

We have characterized and sequenced the variable (V) region genes of the light (L) chains of 10 immunoglobulin (IgM) rheumatoid factor (RF) monoclonal antibodies (MoAb) derived by the hybridoma/Epstein-Barr virus (EBV) technique from the peripheral blood of patients with primary Sjögren's syndrome (pSS). Six out of 10 RFs used lambda (lambda) L chains, while four RFs used kappa (kappa) L chains. Five out of the six lambda RFs were encoded by Vlambda3 gene segments, the sixth one was encoded by a Vlambda1 gene segment. This preferential utilization of the Vlambda3 family genes suggests selective expansion of the B cell in pSS. Three of the kappa RFs used Vkappa3 gene segments, while the fourth used a Vkappa2 gene segment. Half of the RFs were found as unmutated copies of their closest germline (GL) gene. Interestingly these RFs were previously shown to use heavy (H) chains in GL gene configuration. Three RFs have very few mutations (2-3) and only two RFs have substantial numbers of mutations (6 and 11). This also correlated with the number of mutations in the respective H chains. In contrast to RFs in normal and RA these results further suggest the somatic mutation to be of moderate importance in the generation of RF from the peripheral blood of pSS patients.

摘要

我们已对通过杂交瘤/爱泼斯坦-巴尔病毒(EBV)技术从原发性干燥综合征(pSS)患者外周血中获得的10种免疫球蛋白(IgM)类风湿因子(RF)单克隆抗体(MoAb)轻链(L链)的可变(V)区基因进行了表征和测序。10种RF中有6种使用λ(lambda)L链,而4种RF使用κ(kappa)L链。6种λRF中有5种由Vlambda3基因片段编码,第6种由Vlambda1基因片段编码。Vlambda3家族基因的这种优先利用表明pSS中B细胞的选择性扩增。4种κRF中有3种使用Vkappa3基因片段,而第4种使用Vkappa2基因片段。发现一半的RF是其最接近的种系(GL)基因的未突变拷贝。有趣的是,这些RF先前已显示在GL基因构型中使用重链(H链)。3种RF的突变很少(2 - 3个),只有2种RF有大量突变(6个和11个)。这也与各自H链中的突变数量相关。与正常人和类风湿关节炎(RA)中的RF不同,这些结果进一步表明体细胞突变在pSS患者外周血中RF的产生中具有中等重要性。

相似文献

1
Light chain variable (VL) sequences of rheumatoid factors (RF) in patients with primary Sjögren's syndrome (pSS): moderate contribution of somatic hypermutation.原发性干燥综合征(pSS)患者类风湿因子(RF)的轻链可变区(VL)序列:体细胞超突变的中度贡献
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引用本文的文献

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B cells in autoimmune diseases: insights from analyses of immunoglobulin variable (Ig V) gene usage.自身免疫性疾病中的B细胞:来自免疫球蛋白可变区(Ig V)基因使用情况分析的见解
Autoimmun Rev. 2007 Jun;6(6):387-401. doi: 10.1016/j.autrev.2006.12.005. Epub 2007 Jan 12.
2
Abnormalities of B cell phenotype, immunoglobulin gene expression and the emergence of autoimmunity in Sjögren's syndrome.干燥综合征中B细胞表型、免疫球蛋白基因表达异常及自身免疫的出现。
Arthritis Res. 2002;4(6):360-71. doi: 10.1186/ar603. Epub 2002 Sep 25.
3
Genetic aspects of Sjögren's syndrome.
干燥综合征的遗传学方面。
Arthritis Res. 2002;4(6):353-9. doi: 10.1186/ar599. Epub 2002 Sep 24.
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Perturbations in the impact of mutational activity on Vlambda genes in systemic lupus erythematosus.系统性红斑狼疮中突变活性对Vλ基因影响的扰动。
Arthritis Res. 2001;3(6):368-74. doi: 10.1186/ar329. Epub 2001 Sep 14.