Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions.

Journal Article

B cells regulate immune responses by producing antigen-specific antibodies. However, specific B-cell subsets can also negatively regulate T-cell immune responses, and have been termed regulatory B cells. Human and mouse regulatory B cells (B10 cells) with the ability to express the inhibitory cytokine interleukin-10 (IL-10) have been identified. Although rare, B10 cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice. How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.

Full Text

Duke Authors

Cited Authors

  • Yoshizaki, A; Miyagaki, T; DiLillo, DJ; Matsushita, T; Horikawa, M; Kountikov, EI; Spolski, R; Poe, JC; Leonard, WJ; Tedder, TF

Published Date

  • November 8, 2012

Published In

Volume / Issue

  • 491 / 7423

Start / End Page

  • 264 - 268

PubMed ID

  • 23064231

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature11501

Language

  • eng

Conference Location

  • England