Induction of different types of glomerulonephritis by monoclonal antibodies derived from an MRL/lpr lupus mouse.
Induction of different types of glomerulonephritis by monoclonal antibodies derived from an MRL/lpr lupus mouse.
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MRL/lpr 狼疮小鼠单克隆抗体诱导不同类型的肾小球肾炎。
DOI：
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发表时间：
1993
影响因子：
6
通讯作者：
Masahisa Kyogoku
中科院分区：
文献类型：
--
作者：
J. Itoh;Masato Nose;Satoru Takahashi;Masao Ono;S. Terasaki;Emiko Kondoh;Masahisa Kyogoku
MRL/Mp-lpr/lpr（MRL/lpr）狼疮小鼠发生肾小球肾炎，其中疾病的组织病理学表现的特征在于弥漫性细胞增殖、新月体和/或线环样病变，类似于人类狼疮肾炎。虽然这些病变被认为是由抗体介导的，但很少有数据可以解释这些单克隆抗体诱导的肾小球病变的规律性变化。我们研究了正常或严重的联合免疫缺陷小鼠的肾小球病变，这些小鼠注射了产肾炎免疫球蛋白G3的杂交瘤克隆（2B11.3和7B6.8），这些杂交瘤克隆是我们先前从未经操作的MRL/lpr小鼠中建立的。两个克隆引起血清中免疫球蛋白G3水平随时间的增加具有相同的模式，并且都诱导免疫球蛋白G3和C3的肾小球沉积。然而，2B11.3和7B6.8诱导的肾小球病变的组织病理学表现不同。2B11.3克隆产生的细胞增殖性病变与显著的Mac-2阳性巨噬细胞浸润相关，但7B6.8克隆诱导的病变特征在于类似于金属丝环的内皮下透明沉积。后者在病变进展的任何时间点均与显著的炎性细胞浸润无关。因此，我们的研究结果表明，在MRL/lpr小鼠中看到的肾小球肾炎的组织病理学变化的结果从克隆扩增的B细胞克隆，产生不同的致病力的致肾炎抗体。
MRL/Mp-lpr/lpr(MRL/lpr) lupus mice develop glomerulonephritis in which the histopathological manifestations of the disease are characterized by diffuse cell-proliferative, crescentic, and/or wire loop-like lesions, resembling those of human lupus nephritis. Although these lesions are thought to be mediated by antibodies, little data is available to explain these regular variations in glomerular lesions induced by antibodies at the monoclonal level. We studied glomerular lesions of normal or severe combined immunodeficient mice injected with nephritogenic immunoglobulin G3-producing hybridoma clones (2B11.3 and 7B6.8), which we previously established from an unmanipulated MRL/lpr mouse. Both clones caused increased serum levels of immunoglobulin G3 with identical patterns over time and both induced glomerular deposits of immunoglobulin G3 and C3. However, 2B11.3 and 7B6.8 induced glomerular lesions that differed in their histopathological manifestations. The 2B11.3 clone generated cell-proliferative lesions associated with marked Mac-2-positive macrophage infiltrates, but the 7B6.8 clone induced lesions characterized by subendothelial hyaline deposits resembling wire loops. The latter was not associated with significant inflammatory cell infiltrates at any point throughout the progression of the lesion. Thus, our findings suggest that the histopathological variation in glomerulonephritis seen in MRL/lpr mice results from clonally expanded B cell clones that produce nephritogenic antibodies with different pathogenic potencies.
影响因子：
4.4
作者：
M. Ho;T. Springer
通讯作者：
M. Ho;T. Springer