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

Abstract

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.

• Authors: Ayumi Yoshizaki, Tomomitsu Miyagaki, David J DiLillo, Takashi Matsushita, Mayuka Horikawa, Evgueni I Kountikov, Rosanne Spolski, Jonathan C Poe, Warren J Leonard, Thomas F Tedder
• Journal: Nature (Nature) Vol. 491 Issue 7423 Pg. 264-8 (Nov 08 2012) ISSN: 1476-4687 [Electronic] England
• PMID: 23064231 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD19
• CD40 Antigens
• CD5 Antigens
• Histocompatibility Antigens Class II
• Interleukins
• Receptors, Interleukin-21
• Interleukin-10
• interleukin-21

Topics

• Animals
• Antigens, CD19 (genetics, metabolism)
• Autoimmunity (immunology)
• B-Lymphocytes, Regulatory (cytology, immunology, metabolism)
• CD40 Antigens (immunology, metabolism)
• CD5 Antigens (metabolism)
• Cell Division
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology)
• Female
• Histocompatibility Antigens Class II (immunology)
• Humans
• Interleukin-10 (biosynthesis, immunology, metabolism)
• Interleukins (immunology)
• Mice
• Mice, Inbred C57BL
• Multiple Sclerosis (immunology, pathology)
• Receptors, Interleukin-21 (immunology, metabolism)
• T-Lymphocytes (immunology)