Regulatory B Cells Control T Cell Autoimmunity Through IL-21-Dependent Cognate Interactions
By A. Yoshizaki, T. Miyagaki, D. DiLillo, T. Matsushita, Mayuka Horikawa, E. Kountikov, Rosanne Spolski, J. Poe, W. Leonard, T. Tedder. Nature, 2012
617 citations recorded by the source corpus.
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.
Subfields: Immunology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/d549e51ae1db5db272d9ce8c5d46fdf5a952a6b7
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In Immunology
Citations in the corpus
- Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms (2020, background): “Teff cells control neuronal cell function by regulating the production of several pro-inflammatory cytokines and chemokines such as IL-1β, TNF-α, IL-12, CCL2, CCL5, and CXCL10 [136].”
- Regulatory B cells: origin, phenotype, and function. (2015, background): “Other inflammatory cytokines that are known to be critical for Th17 cell differentiation, such as IL-21 (Yoshizaki et al., 2012) and granulocyte macrophage colony-stimulating factor (GM-CSF, in combination with IL-15) (Rafei et al., 2009), have also been shown to be important in Breg cell…”
- CD19+CD24hiCD38hi B Cells Maintain Regulatory T Cells While Limiting TH1 and TH17 Differentiation (2013, background): “It has been recently shown that IL-21 may be a potent inducer of IL-10–producing B cells in mice (40).”
- Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms (2019, background): “Breg cells control antigen-specific T cell autoimmune response through IL-10 production (264).”