A crucial role for B cells in neuroinvasive scrapie
A crucial role for B cells in neuroinvasive scrapie
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DOI：
10.1038/37789
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发表时间：
1997-12-25
期刊：
影响因子：
64.8
通讯作者：
Aguzzi, A
中科院分区：
文献类型：
--
作者：
Klein, MA;Frigg, R;Aguzzi, A
虽然朊病毒蛋白通过脑内接种最有效地繁殖，但外周给药引起了库鲁病、医源性克雅氏病（CJD）、牛海绵状脑病（BSE）和新型变异型克雅氏病（1，2）。外周接种后神经系统疾病的发展取决于淋巴网状系统细胞内朊病毒的扩增（3，4）。在这里，我们调查这些细胞的身份，通过使用一组免疫缺陷小鼠腹腔内接种朊病毒：我们发现，缺陷只影响T淋巴细胞没有明显的影响，但所有的突变，破坏了B淋巴细胞的分化和反应，防止临床瘙痒症的发展。由于缺乏B细胞和抗体与滤泡树突细胞的严重缺陷相关，缺乏这三种成分中的任何一种都可能阻止临床瘙痒症的发展。然而，我们发现，瘙痒症的小鼠外周接种后，表达的免疫球蛋白是专门的M亚类，没有检测到的特异性朊病毒的正常形式的PrPc，并在小鼠分化的B细胞，但没有功能性滤泡树突状细胞。我们的结论是，分化的B细胞是至关重要的神经侵入痒病，无论其受体的特异性。
Although prion proteins are most efficiently propagated through intracerebral inoculation, peripheral administration has caused the diseases kuru, iatrogenic Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE) and new-variant CJD(1,2). The development of neurological disease after peripheral inoculation depends on prion expansion within cells of the lymphoreticular system(3,4). Here we investigate the identity of these cells by using a panel of immune-deficient mice inoculated with prions intraperitoneally: we found that defects affecting only T lymphocytes had no apparent effect, but that all mutations that disrupted the differentiation and response of B lymphocytes prevented the development of clinical scrapie. As an absence of B cells and of antibodies correlates with severe defects in follicular dendritic cells, a lack of any of these three components may prevent the development of clinical scrapie. However, we found that scrapie developed after peripheral inoculation in mice expressing immunoglobulins that were exclusively of the M subclass and without detectable specificity for the normal form of the prion PrPc, and in mice which had differentiated B cells but no functional follicular dendritic cells. We conclude that differentiated B cells are crucial for neuroinvasion by scrapie, regardless of the specificity of their receptors.