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Proinflammatory T helper type 17 cells are effective B-cell helpers
被引:413
|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
来源:
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.
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页码:14292 / 14297
页数:6
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