[HTML][HTML] A fundamental role for interleukin-21 in the generation of T follicular helper cells

A Vogelzang, HM McGuire, D Yu, J Sprent, CR Mackay… - Immunity, 2008 - cell.com
A Vogelzang, HM McGuire, D Yu, J Sprent, CR Mackay, C King
Immunity, 2008cell.com
T cell help to B cells is a fundamental property of adaptive immunity, yet only recently have
many of the cellular and molecular mechanisms of T cell help emerged. T follicular helper
(Tfh) cells are the CD4+ T helper cells that provide cognate help to B cells for high-affinity
antibody production in germinal centers (GC). Tfh cells produce interleukin-21 (IL-21), and
we show that IL-21 was necessary for GC formation. However, the central role of IL-21 in GC
formation reflected its effects on Tfh cell generation rather than on B cells. Expression of the …
Summary
T cell help to B cells is a fundamental property of adaptive immunity, yet only recently have many of the cellular and molecular mechanisms of T cell help emerged. T follicular helper (Tfh) cells are the CD4+ T helper cells that provide cognate help to B cells for high-affinity antibody production in germinal centers (GC). Tfh cells produce interleukin-21 (IL-21), and we show that IL-21 was necessary for GC formation. However, the central role of IL-21 in GC formation reflected its effects on Tfh cell generation rather than on B cells. Expression of the inducible costimulator (ICOS) was necessary for optimal production of IL-21, indicative of interplay between these two Tfh cell-expressed molecules. Finally, we demonstrate that IL-21's costimulatory capacity for T helper cell differentiation operated at the level of the T cell receptor signalosome through Vav1, a signaling molecule that controls T cell helper function. This study reveals a previously unappreciated role for Tfh cells in the formation of the GC and isotype switching through a CD4+ T cell-intrinsic requirement for IL-21.
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