A RHEUMATOID-FACTOR TRANSGENIC MOUSE MODEL OF AUTOANTIBODY REGULATION
A RHEUMATOID-FACTOR TRANSGENIC MOUSE MODEL OF AUTOANTIBODY REGULATION
复制标题
DOI：
10.1093/intimm/5.10.1329
复制
发表时间：
1993-10-01
影响因子：
4.4
通讯作者：
WEIGERT, MG
中科院分区：
文献类型：
--
作者：
SHLOMCHIK, MJ;ZHARHARY, D;WEIGERT, MG
为了解决是否B细胞表达的疾病相关的自身特异性调节正常小鼠，我们已经建立了类风湿因子（RF）转基因模型的自身免疫，使用V基因来源于伊加抗IgG 2a RF分离自自身免疫性MRL/lpr小鼠。由于我们希望研究B细胞发育过程中耐受性的诱导，我们将V（H）基因克隆到IgM表达载体中。我们选择的RF仅结合“a”同种异型的IgG 2a（IgG 2a（a）），但不结合IgG 2a（B），这允许我们在IgH（a）和IgH（B）背景下产生转基因动物，其表达或缺乏自身抗原。研究了两个转基因株系。使用缺乏自身抗原的小鼠，我们通过荧光激活细胞分选和杂交瘤分析表明，在大多数脾B细胞中，H和L转基因被表达以排除内源性基因。尽管有良好的等位基因排除，但遗传上能够表达IgG 2a（a）的转基因小鼠具有降低但显著的（约50 μ g/ml）血清水平。然而，在具有自身抗原的小鼠的外周淋巴器官中表达转基因的B细胞的频率和数量与缺乏自身抗原的小鼠（IgH（B）小鼠）相似。因此，表达抗自身IgG 2a表面受体的B细胞可以在该系统中发育。无论是这样的B细胞无反应性或以其他方式调节自身抗原表达小鼠进行了讨论。
To address whether B cells expressing a disease-associated autospecificity are regulated in normal mice, we have established a rheumatoid factor (RF) transgenic model of autoimmunity, using V genes derived from an IgA anti-IgG2a RF isolated from an autoimmune MRL/lpr mouse. As we wished to study induction of tolerance during B cell development, we cloned the V(H) gene into an IgM expression vector. The RF we chose binds only IgG2a of the 'a' allotype (IgG2a(a)) but not IgG2a(b) allowing us to produce transgenic animals on IgH(a) and IgH(b) backgrounds, which either express or lack the self-antigen. Two transgenic lines were studied. Using mice which lack the self-antigen, we show by fluorescence activated cell sorting and hybridoma analysis that the H and L transgenes are expressed to the exclusion of endogenous genes in most splenic B cells. In spite of good allelic exclusion, transgenic mice which are genetically capable of expressing IgG2a(a) have reduced but significant (approximately 50 mug/ml) serum levels. Nonetheless, the frequency and numbers of transgene-expressing B cells in peripheral lymphoid organs of such mice which have the self-antigen are similar to those which lack it (IgH(b) mice). Thus, B cells expressing an anti-self IgG2a surface receptor can develop in this system. Whether such B cells are anergic or otherwise regulated in autoantigen-expressing mice is discussed.