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

Meike Mitsdoerffer, Youjin Lee, Anneli Jäger, Hye Jung Kim, Thomas Korn, Jay K. Kolls, Harvey Cantor, Estelle Bettellie, Vijay K. Kuchroo

Research output: Contribution to journalArticlepeer-review

424 Scopus citations

Abstract

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 α-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.

Original languageEnglish
Pages (from-to)14292-14297
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number32
DOIs
StatePublished - 10 Aug 2010

Keywords

  • Germinal center
  • IL-17
  • Immunoglobulin
  • Isotype class switching
  • T helper cell

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