Activation of Antiviral Protein Kinase Leads to Immunoglobulin E Class Switching in Human B Cells
Activation of Antiviral Protein Kinase Leads to Immunoglobulin E Class Switching in Human B Cells
复制标题
抗病毒蛋白激酶的激活导致人类 B 细胞中免疫球蛋白 E 类转换
作者：
Kelly J. Rager;J. Langland;B. Jacobs;D. Proud;D. Marsh;F. Imani
摘要病毒感染与哮喘和过敏发作之间的流行病学关联已被证实。此外，来自动物和人类研究的证据表明，在病毒感染期间抗原特异性免疫球蛋白E（IgE）的产生增加，并且IgE水平升高是人类哮喘和过敏的特征。在这里，我们提供了分子证据的作用，病毒感染和激活的抗病毒蛋白激酶（PKR）（双链RNA [dsRNA]激活的蛋白激酶）在诱导IgE类转换。dsRNA（病毒感染的已知组分和PKR的激活剂）的存在诱导IgE类别转换，如通过人拉莫斯B细胞系中生殖系IgE的表达所检测的。此外，dsRNA处理拉莫斯细胞导致PKR的激活和NF-κB复合物的体内激活。有趣的是，用鼻病毒（普通感冒病毒）血清型14和16感染拉莫斯细胞导致生殖系hepatitis B表达的诱导。为了进一步评估PKR在病毒诱导IgE类别转换中的作用，我们用两种不同的牛痘病毒（牛痘病毒）株感染拉莫斯细胞。感染野生型牛痘病毒未能诱导生殖细胞表达，然而，缺失突变体的牛痘病毒（VP 1080）缺乏PKR抑制多肽E3 L诱导生殖细胞表达。总的来说，我们的研究结果定义了一个共同的分子机制，潜在的作用，病毒感染的IgE类转换和随后的诱导IgE介导的疾病，如过敏和哮喘。
ABSTRACT An epidemiologic association between viral infections and the onset of asthma and allergy has been documented. Also, evidence from animal and human studies has suggested an increase in antigen-specific immunoglobulin E (IgE) production during viral infections, and elevated levels of IgE are characteristic of human asthma and allergy. Here, we provide molecular evidence for the roles of viral infection and of activation of the antiviral protein kinase (PKR) (double-stranded-RNA [dsRNA]-activated protein kinase) in the induction of IgE class switching. The presence of dsRNA, a known component of viral infection and an activator of PKR, induced IgE class switching as detected by the expression of germ line ɛ in the human Ramos B-cell line. Furthermore, dsRNA treatment of Ramos cells resulted in the activation of PKR and in vivo activation of the NF-κB complex. Interestingly, infection of Ramos cells with rhinovirus (common cold virus) serotypes 14 and 16 resulted in the induction of germ line ɛ expression. To further evaluate the role of PKR in the viral induction of IgE class switching, we infected Ramos cells with two different vaccinia virus (cowpox virus) strains. Infection with wild-type vaccinia virus failed to induce germ line ɛ expression; however, a deletion mutant of vaccinia virus (VP1080) lacking the PKR-inhibitory polypeptide E3L induced the expression of germ line ɛ. Collectively, the results of our study define a common molecular mechanism underlying the role of viral infections in IgE class switching and subsequent induction of IgE-mediated disorders such as allergy and asthma.
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DOI：
10.1073/pnas.89.11.4825
发表时间：
1992-06-01
影响因子：
11.1
作者：
CHANG, HW;WATSON, JC;JACOBS, BL
通讯作者：
JACOBS, BL
影响因子：
3.7
作者：
LU, Y;WAMBACH, M;KRUG, RM
通讯作者：
KRUG, RM
病毒疫苗增强了狗体内针对花粉的免疫球蛋白 E 抗体。
影响因子：
1
作者：
Frick,OL;Brooks,DL
通讯作者：
Brooks,DL
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Miyamoto,NG;Jacobs,BL;Samuel,CE
通讯作者：
Samuel,CE
DOI：
--
发表时间：
1979-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Minks;D. West;S. Benvin;C. Baglioni
通讯作者：
M. Minks;D. West;S. Benvin;C. Baglioni