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Modulation of the humoral immune response by constitutively active STAT6 expression in murine B cells.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2019-12-15 , DOI: 10.1002/eji.201948313
Paul Haase 1 , Lavanya Mokada-Gopal 1 , Daniel Radtke 1 , David Voehringer 1
Affiliation  

The transcription factor STAT6 regulates gene expression in response to IL-4 and IL-13. To further investigate how activated STAT6 modulates B cells development and function in vivo, we characterized mice that express a constitutively active version specifically in B cells. CD19Cre_STAT6vt mice show spontaneous phosphorylation and nuclear translocation of STAT6 in B cells. About 80 genes were more than twofold up- or downregulated in splenic B cells from CD19Cre_STAT6vt as compared to control mice. B cell development, tissue localization, and populations of follicular and marginal zone B cells, B1 B cells, GC B cells, and plasma cells (PCs) appeared to be normal. However, the number of IgE+ and IgG1+ GC B cells and PCs as well as serum IgE and IgG1 levels were increased in CD19Cre_STAT6vt mice. Infection with Lymphocytic choriomeningitis virus associated with high levels of TNF and IFN-γ did not prevent the development of a significantly increased IgE and IgG1 response against the virus in CD19Cre_STAT6vt mice. These results suggest that prolonged STAT6 activation during chronic allergic inflammation may result in IgE responses during subsequent viral or bacterial infection that could further stimulate mast cell activation even in the absence of the initial allergic response.

中文翻译:

在鼠B细胞中通过组成性活性STAT6表达来调节体液免疫应答。

转录因子STAT6响应IL-4和IL-13调节基因表达。为了进一步研究活化的STAT6如何在体内调节B细胞的发育和功能,我们表征了在B细胞中特异表达组成型活性形式的小鼠。CD19Cre_STAT6vt小鼠在B细胞中显示出STAT6的自发磷酸化和核易位。与对照小鼠相比,来自CD19Cre_STAT6vt的脾B细胞中约有80个基因被上调或下调了两倍以上。B细胞发育,组织定位以及滤泡和边缘区B细胞,B1 B细胞,GC B细胞和浆细胞(PC)的数量似乎是正常的。但是,CD19Cre_STAT6vt小鼠的IgE +和IgG1 + GC B细胞和PC数量以及血清IgE和IgG1水平增加。在CD19Cre_STAT6vt小鼠中,与高水平的TNF和IFN-γ相关的淋巴细胞性脉络膜脑膜炎病毒感染并不能阻止针对该病毒的IgE和IgG1应答明显增加。这些结果表明,在慢性变态反应性炎症过程中延长的STAT6激活可能导致随后的病毒或细菌感染过程中的IgE反应,甚至在没有初始变态反应的情况下也可能进一步刺激肥大细胞激活。
更新日期:2019-12-15
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