| First Author | Yang Z | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 5 | PubMed ID | 32130409 |
| Mgi Jnum | J:289403 | Mgi Id | MGI:6432530 |
| Doi | 10.1084/jem.20190472 | Citation | Yang Z, et al. (2020) IL-21 is a broad negative regulator of IgE class switch recombination in mouse and human B cells. J Exp Med 217(5) |
| abstractText | 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-gamma, 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. |
