Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules
Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules
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DOI：
10.1093/intimm/12.9.1275
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发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Zinkernagel, RM
中科院分区：
文献类型：
--
作者：
Fehr, T;López-Macías, C;Zinkernagel, RM
本研究试图评估和比较各种B细胞特异性标记物在缺乏a细胞受体（BCR）复合物分子的小鼠品系中抗病毒免疫应答的作用（IgM、IG（alpha）和C-kappa），共刺激分子（CD 19和CD 22）、蛋白激酶[布鲁顿酪氨酸激酶（Btk）]或转录因子（OBF-1），使用T细胞非依赖性（TI）或T细胞依赖性（TD）抗原在两种模型感染[水泡性口炎病毒（VSV）和淋巴细胞性脉络丛脑膜炎病毒（LCMV）]中对这些小鼠进行了测试。所有小鼠均控制LCMV感染，表明细胞毒性T细胞功能在正常范围内。相比之下，OBF-1（-/-）小鼠受到部分保护，mb-1（Delta c/Delta c）小鼠完全没有受到VSV感染的保护，VSV感染是一种几乎完全由中和抗体控制的病毒。对VSV感染的易感性与脾脏结构缺陷相关：缺乏成熟的α细胞和具有边缘区巨噬细胞的滤泡，缺乏具有滤泡树突状细胞的生发中心，分别与缺乏或显著减少保护性IgM和IgG反应相关。κ轻链的缺乏不影响中和反应，表明它可以很容易地被λ链取代。缺乏共刺激分子CD 19和CD 22或信号分子Btk具有调节作用，但不增加对VSV或LCMV的易感性。我们的研究结果表明，在信号级联反应的开始（BCR复合物）和结束（转录），细胞活化有关键的分子，而调节两者之间反应的微调因子表现出相当大的功能重叠。
This study attempted to evaluate and compare the role of various B cell-specific markers for antiviral immune responses in mouse strains lacking molecules belonging to the a cell receptor (BCR) complex (IgM, Ig(alpha) and C-kappa), the co-stimulatory molecules (CD19 and CD22), the protein kinases [Bruton's tyrosine kinase (Btk)] or the transcription factors (OBF-1), These mice were tested in two model infections [vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV)] using T cell-independent (TI) or T cell-dependent (TD) antigens. All mice controlled an LCMV infection indicating that cytotoxic T cell functions were within normal ranges. In contrast, OBF-1(-/-) mice were partially protected and mb-1(Delta c/Delta c) mice not at all protected against VSV infection, a virus that is controlled virtually exclusively by neutralizing antibodies. Susceptibility to VSV infection was correlated with structural defects in the spleen: absence of mature a cells and follicles with marginal zone macrophages and absence of germinal centers with follicular dendritic cells correlated with lack or substantial reduction of protective IgM and IgG responses respectively. The lack of kappa light chain did not affect the neutralizing response, indicating that it could easily be replaced by the lambda chain. Absence of the co-stimulatory molecules CD19 and CD22 or of the signaling molecule Btk had modulating effects, but did not increase susceptibility to VSV or LCMV. Our findings suggest that there are crucial molecules for a cell activation at the beginning (BCR complex) and the end (transcription) of the signaling cascade, whereas fine-tuning factors modulating the response in between exhibit considerable functional overlap.