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

Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14292-7. doi: 10.1073/pnas.1009234107. Epub 2010 Jul 26.

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 alpha-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Proliferation
  • Immunoglobulin Class Switching
  • Immunoglobulin Isotypes / analysis
  • Inflammation / immunology
  • Interleukin-17 / immunology*
  • Mice
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Immunoglobulin Isotypes
  • Interleukin-17