Hamilton Jennie A, Wu Qi, Yang PingAr, Luo Bao, Liu Shanrun, Hong Huixian, Li Jun, Walter Mark R, Fish Eleanor N, Hsu Hui-Chen, Mountz John D
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294.
J Immunol. 2017 Oct 15;199(8):2618-2623. doi: 10.4049/jimmunol.1700888. Epub 2017 Sep 13.
The transitional stage of B cell development is a formative stage in the spleen where autoreactive specificities are censored as B cells gain immune competence, but the intrinsic and extrinsic factors regulating survival of transitional stage 1 (T1) B cells are unknown. We report that B cell expression of IFN-β is required for optimal survival and TLR7 responses of transitional B cells in the spleen and was overexpressed in T1 B cells from BXD2 lupus-prone mice. Single-cell gene expression analysis of B6 versus B6 T1 B cells revealed heterogeneous expression of in wild-type B cells and distinct gene expression patterns associated with endogenous IFN-β. Single-cell analysis of BXD2 T1 B cells revealed that is expressed in early T1 B cell development with subsequent upregulation of and Together, these data suggest that T1 B cell expression of IFN-β plays a key role in regulating responsiveness to external factors.
B细胞发育的过渡阶段是脾脏中的一个形成阶段,在此阶段,随着B细胞获得免疫能力,自身反应性特异性会受到审查,但调节1期过渡性(T1)B细胞存活的内在和外在因素尚不清楚。我们报告称,脾脏中过渡性B细胞的最佳存活和TLR7反应需要B细胞表达IFN-β,并且在易患狼疮的BXD2小鼠的T1 B细胞中IFN-β表达上调。对B6与B6 T1 B细胞进行单细胞基因表达分析,揭示了野生型B细胞中IFN-β的异质性表达以及与内源性IFN-β相关的不同基因表达模式。对BXD2 T1 B细胞进行单细胞分析发现,IFN-β在早期T1 B细胞发育中表达,随后IFN-α和IFN-γ上调。总之,这些数据表明,T1 B细胞表达的IFN-β在调节对外界因素的反应性中起关键作用。