allergic diseases

ige synthesis

il production

Journal of Experimental Medicine

IgE antibodies may elicit potent allergic reactions, and their production is tightly controlled. The tendency to generate IgE has been thought to reflect the balance between type 1 and type 2 cytokines, with the latter promoting IgE. Here, we reevaluated this paradigm by a direct cellular analysis, demonstrating that IgE production was not limited to type 2 immune responses yet was generally constrained in vivo. IL-21 was a critical negative regulator of IgE responses, whereas IFN-γ, IL-6, and IL-10 were dispensable. Follicular helper T cells were the primary source of IL-21 that inhibited IgE responses by directly engaging the IL-21 receptor on B cells and triggering STAT3-dependent signaling. We reconciled previous discordant results between mouse and human B cells and revealed that the inhibition of IgE class switch recombination by IL-21 was attenuated by CD40 signaling, whereas IgG1 class switch recombination was potentiated by IL-21 in the context of limited IL-4. These findings establish key features of the extrinsic regulation of IgE production by cytokines.

IL-21 is a broad negative regulator of IgE class switch recombination in mouse and human B cells