| 李慧1# 段涛2# 冯海瑕1 刘玉峰1 李巍1△.Notch 信号途径在Bregs发育及口服耐受中的作用*[J].,2014,14(15):2844-2847 |
| Notch 信号途径在Bregs发育及口服耐受中的作用* |
| Notch Signal Pathway in Bregs Development and Oral Tolerance* |
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| DOI： |
| 中文关键词: Bregs IL-10 Notch 信号途径 口服耐受 |
| 英文关键词: RegulatoryB cell IL-10 Notch signaling pathway Oral tolerance |
| 基金项目:国家自然科学基金项目(81273320) |
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| 中文摘要: |
| 摘要目的：调节性B细胞(Bregs)是近年来确认的一类具有负向免疫调节功能的B细胞亚群，在免疫反应中通过IL-10 发挥调节
功能，又称为B10 细胞，其表型为CD19+CD5+CD1dhigh，在多种疾病中发挥重要的调节作用，但关于Bregs 的发育及发挥调节功
能的具体机制尚不明确。Notch 信号途径是调控细胞双向亚群和双向功能分化的重要信号途径，在T/B 细胞分化、CD4/CD8 细胞
等细胞发育中发挥重要的作用，但其在B10 细胞发育及其免疫应答中调控作用尚不明确。本研究利用特异性在B 细胞剔除
Notch 信号分子RBP-J 基因的小鼠，分析Notch信号对Bregs发育及口服耐受的影响。方法：将CD19-Cre 小鼠与RBP-Jflox 小鼠
交配，获得CD19-Cre/RBP-Jf/f 基因型小鼠，流式细胞仪分析该小鼠CD19+CD5+CD1dhighB10 细胞及体外刺激后产生IL-10 的
B10 细胞数量；制备口服免疫耐受模型，分析Notch 信号缺失对B10细胞发育和功能的影响。结果：B细胞特异性敲除RBP-J 基
因的小鼠的CD19+CD5+CD1dhighBregs 数量及体外刺激后产生IL-10 的B10 细胞数量比杂合子小鼠显著降低；且在口服免疫耐
受模型中血清IgE 水平显著升高。结论：Notch 信号敲除后，脾脏Bregs 及其产生IL-10 减少，在口服耐受中不能产生耐受，Notch
信号可能促进Bregs发育，并通过IL-10参与调控口服耐受。 |
| 英文摘要: |
| ABSTRACT Objective:RegualtoryB cell (Bregs) is a specific B cell population potently inhibits immune responses through the secretion
of IL-10 recent years, termed B10 cells also. Its phenotype is CD5+CD1dhighCD19+. Bregs play an important role in several diseases.
However, the precise mechanisms of Bregs development has not been elucidated so far. Notch signaling pathway participated in
regulating cell subsets and bi functional differentiation. It involved in T/B cell and CD4/CD8 T cell differentiation It is not clear that
Notch signaling pathway regulates B10 development and immune response. We will focus on analysis of the role of Notch signal pathway
on Bregs cell development and the regulation on Breg in oral immune tolerance in a class of transgenic mice, in which the RBP-J
gene were inactiveed in B cells. Methods:We acquired the CD19-cre/RBP-Jflox/flox genotype mice by mating the CD19-cre mice and
RBP-Jflox mice, analysis of the frequencies of CD19+Cd5+CD1dhigh Bregs and IL-10-producing B10 cell after stimu by Flow cytometric.
Preparation of oral immune tolerance model to analyse of Notch signaling pathway effect on Bregs function. Results:The frequencies of
CD19+CD5+CD1dhigh Bregs were significantly reduced in CD19-cre-RBP-Jf/f mice compared with the heteroaygous mice, the level of
IgE increased in the mice which B cell specific knockout RBP-J. Conclusion:The numbers of Bregs and IL-10-producing decreased,
which B cell specific knockout RBP-J can not tolerance in oral immune tolerance. Noch signaling pathway promotes Bregs development
and controls oral tolerance by mediating IL-10. |
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