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
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
相关论文
共 50 条
  • [21] B-CELL HELPER FACTORS
    LEIBSON, HJ
    ENDRES, R
    ROEHM, N
    ZLOTNIK, A
    MARRACK, P
    KAPPLER, JW
    FEDERATION PROCEEDINGS, 1983, 42 (04) : 1072 - 1072
  • [22] REGULATION BY NORMAL T-HELPER CELLS OF B-CELL LYMPHOMA CELL-CYCLE PROGRESSION
    REID, SL
    SNOW, EC
    JOURNAL OF CELLULAR BIOCHEMISTRY, 1995, : 176 - 176
  • [23] B-cell activation in vitro by helper T cells specific to a protein region that is recognized both by T cells and by antibodies
    Hamajima, S
    Atassi, MZ
    IMMUNOLOGICAL INVESTIGATIONS, 1998, 27 (03) : 121 - 134
  • [24] T-CELL REGULATION OF POLYCLONAL B-CELL RESPONSIVENESS .I. HELPER EFFECTS OF T-CELLS
    GOODMAN, MG
    WEIGLE, WO
    JOURNAL OF IMMUNOLOGY, 1979, 122 (06): : 2548 - 2553
  • [25] B-CELL TRANSPLANTS TO IMMUNODEFICIENT XID NEONATES DO NOT IMPRINT THEIR HELPER T-CELLS
    QUINTANS, J
    WEMHOFF, GA
    JOURNAL OF MOLECULAR AND CELLULAR IMMUNOLOGY, 1988, 4 (02): : 97 - 103
  • [26] CONTACT WITH HELPER T-CELLS DOES NOT LIMIT THE INDUCTION OF RESTING B-CELL DIFFERENTIATION
    JULIUS, MH
    LOUSTE, K
    PROGRESS IN IMMUNOLOGY, VOL 7, 1989, : 587 - 592
  • [27] B-CELL DIFFERENTIATION IN SPLENIC ENVIRONMENT - ACQUIRED SUSCEPTIBILITY TO HELPER FUNCTION OF IRRADIATED T CELLS
    ITO, T
    KINO, T
    CUDKOWICZ, G
    JOURNAL OF IMMUNOLOGY, 1973, 110 (02): : 596 - 599
  • [28] USE OF CLONED T-HELPER CELLS FOR THE DISSECTION OF SIGNALS INVOLVED IN B-CELL ACTIVATION
    ZUBLER, RH
    GLASEBROOK, AL
    REICH, U
    IMMUNOBIOLOGY, 1981, 160 (01) : 140 - 140
  • [29] Diffuse Large B-cell Lymphoma Involving an Abundant Infiltration of T Follicular Helper Cells
    Ishii, Keitaro
    Kamachi, Kazuharu
    Okamoto, Sho
    Katsuya, Hiroo
    Fujita, Mai
    Nagaie, Toshiaki
    Nishioka, Atsujiro
    Yoshimura, Mariko
    Ureshino, Hiroshi
    Kubota, Yasushi
    Ando, Toshihiko
    Watanabe, Tatsuro
    Takeuchi, Mai
    Kai, Keita
    Ohshima, Koichi
    Kimura, Shinya
    INTERNAL MEDICINE, 2023, 62 (09) : 1335 - 1340
  • [30] STIMULATION OF A MEMORY B-CELL RESPONSE DOES NOT REQUIRE PRIMED HELPER T-CELLS
    LECLERC, C
    SEDLIK, C
    LOMAN, R
    CHARLOT, B
    ROJAS, M
    DERIAUD, E
    EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (09) : 2533 - 2538