Proinflammatory T helper type 17 cells are effective B-cell helpers

被引:414
作者
Mitsdoerffer, Meike [2 ]
Lee, Youjin [2 ]
Jaeger, Anneli [2 ]
Kim, Hye-Jung [1 ]
Korn, Thomas [3 ]
Kolls, Jay K. [4 ]
Cantor, Harvey [1 ]
Bettelli, Estelle [5 ]
Kuchroo, Vijay K. [2 ]
机构
[1] Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA
[3] Tech Univ Munich, Dept Neurol, D-81675 Munich, Germany
[4] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA
[5] Benaroya Res Inst, Seattle, WA 98101 USA
基金
美国国家卫生研究院;
关键词
germinal center; IL-17; immunoglobulin; isotype class switching; T helper cell; IN-VIVO; IL-21; DIFFERENTIATION; GENERATION; RESPONSES; PLASTICITY; RECEPTOR; LINEAGE; IL-17; TH1;
D O I
10.1073/pnas.1009234107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
T helper type 17 (TH17) cells are highly proinflammatory effector T cells that are characterized by the production of high amounts of IL-17A, IL-17F, IL-21, and IL-22. Furthermore, TH17 cells have been associated with a number of autoimmune diseases. However, it is not clear whether TH17 cells can also serve as effective helper cells. Here we show that TH17 cells can function as B-cell helpers in that they not only induce a strong proliferative response of B cells in vitro but also trigger antibody production with class switch recombination in vivo. Transfer of TH17 cells into WT or T-cell receptor a-deficient mice, which lack endogenous T cells, induces a pronounced antibody response with preferential isotype class switching to IgG1, IgG2a, IgG2b, and IgG3, as well as the formation of germinal centers. Conversely, blockade of IL-17 signaling results in a significant reduction in both number and size of germinal centers. Whereas IL-21 is known to help B cells, IL-17 on its own drives B cells to undergo preferential isotype class switching to IgG2a and IgG3 subtypes. These observations provide insights into the unappreciated role of TH17 cells and their signature cytokines in mediating B-cell differentiation and class switch recombination.
引用
收藏
页码:14292 / 14297
页数:6
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