期刊
CELL REPORTS
卷 28, 期 7, 页码 1758-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.07.034
关键词
-
类别
资金
- National Health and Medical Research Council (NHMRC) [GNT1137989, GNT1057707, GNT1006592, GNT1045549, GNT1065626]
- NIH [R01 AI107020, R21 AI124143]
- University of Melbourne research scholarship
- Australian Research Council Future Fellowship [FT130100708]
- NHMRC Career Development Fellowship [1108066]
- NHMRC Senior Principal Research Fellowship
- Sylvia & Charles Viertel Senior Medical Research Fellowship
- Biomedicine Discovery Institute Scholarship from Monash University
- Walter and Eliza Hall Centenary Fellowship - CSL
- Bellberry-Viertel Senior Medical Research Fellowship
- National Health and Medical Research Council of Australia [1108066] Funding Source: NHMRC
- Australian Research Council [FT130100708] Funding Source: Australian Research Council
Following infection, inflammatory cues upregulate core transcriptional programs to establish pathogen-specific protection. In viral infections, T follicular helper (TFH) cells express the prototypical T helper 1 transcription factor T-bet. Several studies have demonstrated essential but conflicting roles for T-bet in TFH biology. Understanding the basis of this controversy is crucial, as modulation of T-bet expression instructs TFH differentiation and ultimately protective antibody responses. Comparing influenza and LCMV viral infections, we demonstrate that the role of T-bet is contingent on the environmental setting of TFH differentiation, IL-2 signaling, and T cell competition. Furthermore, we demonstrate that T-bet expression by either TFH or GC B cells independently drives antibody isotype class switching. Specifically, T cell-specific loss of T-bet promotes IgG1, whereas B cell-specific loss of T-bet inhibits IgG2a/c switching. Combined, this work highlights that the context-dependent induction of T-bet instructs the development of protective, neutralizing antibodies following viral infection or vaccination.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据