Cutting Edge: IL-4, IL-21, and IFN-γ Interact To Govern T-bet and CD11c Expression in TLR-Activated B Cells

被引:188
作者
Naradikian, Martin S. [1 ,2 ]
Myles, Arpita [1 ,2 ]
Beiting, Daniel P. [2 ,3 ]
Roberts, Kenneth J. [1 ]
Dawson, Lucas [2 ,3 ]
Herati, Ramin Sedaghat [2 ,4 ]
Bengsch, Bertram [2 ,5 ]
Linderman, Susanne L. [2 ,5 ,6 ]
Stelekati, Erietta [2 ,5 ]
Spolski, Rosanne [7 ,8 ]
Wherry, E. John [2 ,5 ]
Hunter, Christopher [2 ,3 ]
Hensley, Scott E. [2 ,5 ,6 ]
Leonard, Warren J. [7 ,8 ]
Cancro, Michael P. [1 ,2 ]
机构
[1] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA
[5] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA
[6] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA
[7] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA
[8] NHLBI, Ctr Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA
关键词
FOLLICULAR HELPER-CELLS; TRANSCRIPTION FACTOR; MEMORY; EXPANSION; RECEPTOR; INFECTION; RESPONSES; ANTIGEN;
D O I
10.4049/jimmunol.1600522
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T-bet and CD11c expression in B cells is linked with IgG(2c) isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing T-bet and CD11c expression in B cells remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-gamma that regulates T-bet expression in B cells. We find that IL-21 or IFN-gamma directly promote T-bet expression in the context of TLR engagement. Further, IL-4 antagonizes T-bet induction. Finally, IL-21, but not IFN-gamma, promotes CD11c expression independent of T-bet. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether T-bet(+) and CD11c(+) B cells are formed. These findings suggest that T-bet(+) B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu.
引用
收藏
页码:1023 / 1028
页数:6
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