Proinflammatory T helper type 17 cells are effective B-cell helpers.
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.
Mitsdoerffer
Meike
M
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Lee
Youjin
Y
Jäger
Anneli
A
Kim
Hye-Jung
HJ
Korn
Thomas
T
Kolls
Jay K
JK
Cantor
Harvey
H
Bettelli
Estelle
E
Kuchroo
Vijay K
VK
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D007132:Immunoglobulin Isotypes; D020381:Interleukin-17