Essential role of IL-21 in B cell activation, expansion, and plasma cell generation during CD4+ T cell-B cell collaboration

S Kuchen, R Robbins, GP Sims, C Sheng… - The journal of …, 2007 - journals.aai.org
S Kuchen, R Robbins, GP Sims, C Sheng, TM Phillips, PE Lipsky, R Ettinger
The journal of immunology, 2007journals.aai.org
During T cell-B cell collaboration, plasma cell (PC) differentiation and Ig production are
known to require T cell-derived soluble factors. However, the exact nature of the cytokines
produced by activated T cells that costimulate PC differentiation is not clear. Previously, we
reported that costimulation of purified human B cells with IL-21 and anti-CD40 resulted in
efficient PC differentiation. In this study, we addressed whether de novo production of IL-21
was involved in direct T cell-induced B cell activation, proliferation, and PC differentiation …
Abstract
During T cell-B cell collaboration, plasma cell (PC) differentiation and Ig production are known to require T cell-derived soluble factors. However, the exact nature of the cytokines produced by activated T cells that costimulate PC differentiation is not clear. Previously, we reported that costimulation of purified human B cells with IL-21 and anti-CD40 resulted in efficient PC differentiation. In this study, we addressed whether de novo production of IL-21 was involved in direct T cell-induced B cell activation, proliferation, and PC differentiation. We found that activated human peripheral blood CD4+ T cells expressed mRNA for a number of cytokines, including IL-21, which was confirmed at the protein level. Using a panel of reagents that specifically neutralize cytokine activity, we addressed which cytokines are essential for B cell activation and PC differentiation induced by anti-CD3-activated T cells. Strikingly, neutralization of IL-21 with an IL-21R fusion protein (IL-21R-Fc) significantly inhibited T cell-induced B cell activation, proliferation, PC differentiation, and Ig production. Inhibition of PC differentiation was observed even when the addition of IL-21R-Fc was delayed until after initial B cell activation and expansion had occurred. Importantly, IL-21 was found to be involved in PC differentiation from both naive and memory B cells. Finally, IL-21R-Fc did not inhibit anti-CD3-induced CD4+ T cell activation, but rather directly blocked T cell-induced B cell activation and PC differentiation. These data are the first to document that B cell activation, expansion, and PC differentiation induced by direct interaction of B cells with activated T cells requires IL-21.
journals.aai.org