A Genetic Locus Controlling Aging‐sensitive Regression of B Lymphopoiesis in an Autoimmune‐prone MRL/lpr Strain of Mice
A Genetic Locus Controlling Aging‐sensitive Regression of B Lymphopoiesis in an Autoimmune‐prone MRL/lpr Strain of Mice
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DOI：
10.1111/j.1365-3083.2007.02020.x
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发表时间：
2007-12
影响因子：
3.7
通讯作者：
K. Nakatani;W. Qu;M-C Zhang;H. Fujii;H. Furukawa;T. Miyazaki;M. Iwano;Y. Saito;M. Nose;M. Ono
中科院分区：
文献类型：
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作者：
K. Nakatani;W. Qu;M-C Zhang;H. Fujii;H. Furukawa;T. Miyazaki;M. Iwano;Y. Saito;M. Nose;M. Ono
衰老很容易在环境和/或内在因素的影响下影响免疫系统，同时加速包括自身免疫性疾病在内的各种免疫疾病的发展。免疫衰老与自身免疫性疾病的发生发展之间的分子和细胞机制知之甚少。在这里，我们首先展示了一种易患狼疮的MRL/Mp.Faslpr(MRL/LPR)小鼠的品系特异性和对衰老敏感的B细胞异常的开始。这种异常的特征是该菌株骨髓中B淋巴细胞的倒退。接下来，我们研究了老年(MRL/LPR×C3H/He.Faslpr)F2小鼠B细胞退化与自身免疫性疾病发病之间的关系，在F2小鼠中，肾小球肾炎、血管炎、涎腺炎和关节炎等病理表型发生了不同程度的发展。我们还使用相同的F2小鼠进行全基因组搜索，以确定与B细胞回归相关的遗传位点。采用逆转录酶-聚合酶链式反应(RT-PCR)技术，对F2代小鼠脾组织中B细胞退行性变进行了回顾性研究。结果表明，F2小鼠自身免疫性疾病的发生与衰老敏感型B细胞退化无关。遗传研究确定了D5Mit233(29 CM)附近的一个重要的B细胞退化的基因座。这是第一个证据表明存在一个遗传位点，它以一种对衰老敏感的方式影响B淋巴细胞的生成。
Aging readily affects immune system under the influence of environmental and/or intrinsic factors while accelerating the development of various immune disorders including autoimmune diseases. Little is known about molecular and cellular mechanisms connecting between immune senescence and development of autoimmune diseases. Here, we first show strain‐specific and aging‐sensitive onset of B‐cell abnormality in a lupus‐prone MRL/Mp.Faslpr (MRL/lpr) strain of mice. This abnormality was characterized by the regression of B lymphopoiesis in the bone marrow of this strain. We next examined the association between the B‐cell regression and onset of autoimmune diseases in aged (MRL/lpr × C3H/He.Faslpr) F2 mice, in which pathologic phenotypes, such as glomerulonephritis, vasculitis, sialoadenitis and arthritis, variously developed. We also searched whole genome to identify genetic loci linked to the B‐cell regression by using the same F2 mice. The B‐cell regression manifested in the spleen of F2 mice was retrospectively evaluated by reverse transcriptase‐based PCR quantification. The results demonstrated that the onset of autoimmune diseases in the F2 mice was not associated with the aging‐sensitive B‐cell regression. The genetic study identified a significant locus responsible for the B‐cell regression in the vicinity of D5Mit233 (29 cM). This is first evidence for the presence of a genetic locus that affects B lymphopoiesis in an aging‐sensitive manner.