Prevention of Arthritis by Interleukin 10–producing B Cells

Mauri, Claudia; Gray, David; Mushtaq, Naseem; Londei, Marco

doi:10.1084/jem.20021293

Cited by 763 publications

(718 citation statements)

References 33 publications

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“…A common mechanism to explain the induction of T cell tolerance by B cells is IL-10 secretion. Examples include chronic intestinal inflammation (32), arthritis (33), autoimmunity (34), and ileitis (35). The IL-10-secreting B cell that we find in the draining lymph node of UV-irradiated mice is yet one more example that can be added to a growing list of immunoregulatory B cells.…”

Section: Discussionmentioning

confidence: 99%

A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells

Matsumura

Byrne

Nghiem

et al. 2006

The Journal of Immunology

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UV exposure suppresses the immune response to a variety of microbial, fungal, and viral Ags. In addition, UV radiation is a complete carcinogen and the immune suppression induced by UV radiation is a major risk factor for skin cancer induction. In this study, we examined the mechanisms underlying the induction of immune suppression and tolerance induction by UV radiation. Transferring lymph nodes cells from UV-irradiated, FITC-sensitized mice into normal recipients transferred immune tolerance. Contrary to expectations, the cell responsible was an FITC+, IL-10-secreting, CD19+, B220+ B cell. Because the lipid mediator of inflammation, platelet-activating factor (PAF) is released by UV-irradiated keratinocytes and is essential for the induction of immune suppression, we determined its role in tolerance induction. When UV-irradiated mice were injected with PCA 4248, a selective PAF receptor (PAFR) antagonist, transfer of tolerance was suppressed. However, immune suppression was not transferred when FITC+ cells from the draining lymph nodes of UV-irradiated, PAFR-deficient donor mice were injected into the recipients. Because PCA 4248 also blocks serotonin receptor binding, we measured the effect that blocking both serotonin and PAFR binding has on the transfer of immune suppression. Only when both PAF and serotonin binding were blocked could we inhibit tolerance induction. These data identify a novel function for PAF and serotonin in modulating immune function, the activation of immunoregulatory B cells.

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Section: Discussionmentioning

confidence: 99%

A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells

Matsumura

Byrne

Nghiem

et al. 2006

The Journal of Immunology

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“…Activation of arthritogenic splenocytes with Ag and agonistic anti-CD40 mAb induces a B cell population that produces high levels of IL-10 and low levels of IFNγ [85]. The adoptive transfer of these B cells into DBA/1--T cell receptor--β-Tg mice, immunized with bovine collagen (type II collagen) emulsified in complete Freund's adjuvant, inhibits T H1 responses, prevents arthritis development, and is effective in ameliorating established disease.…”

Section: B10 Cells In Mouse Models Of Autoimmune Diseasementioning

confidence: 99%

“…B10 cells can be expanded for therapeutic purposes either in vivo or ex vivo . Expansion of B10 cells in vivo by means of agonistic CD40 antibody has shown benefit in CIA [85]. However, expanding B10 cells in vivo carries additional risks since the currently identified stimuli driving B10 cell development are rather nonspecific and, if administered systemically, will trigger responses in a variety of immune cells.…”

Section: Therapeutic Potential Of B10 Cellsmentioning

confidence: 99%

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

2013

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B cell abnormalities contribute to the development and progress of autoimmune disease. Traditionally, the role of B cells in autoimmune disease was thought to be predominantly limited to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and activation of T cells, expression of co-stimulatory molecules and cytokine production. Recently, the ability of B cells to negatively regulate cellular immune responses and inflammation has been described and the concept of regulatory B cells has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported, with IL-10 being the most studied. In this review, this specific IL-10-producing subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through different mechanisms. B10 cells are a functionally defined subset currently identified only by their competency to produce and secrete IL-10 following appropriate stimulation. Although B10 cells share surface markers with other previously defined B cell subsets, currently there is no cell surface or intracellular phenotypic marker or set of markers unique to B10 cells. The recent discovery of an effective way to expand B10 cells ex vivo opens new horizons in the potential therapeutic applications of this rare B cell subset. This review highlights the current knowledge on B10 cells and discusses their potential as novel therapeutic agents in autoimmunity.

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“…A regulatory CD1d hi CD5+ B cell that produces interleukin (IL)‐10 controls T cell‐dependent inflammatory responses 5. Regulatory B cells producing IL‐10 have also been shown to suppress inflammatory disorders including arthritis, allergy, ulcerative colitis, and experimental autoimmune encephalomyelitis 6, 7, 8. IL10, a potent anti‐atherogenic cytokine,9 is critical for sustaining the expansion of CD5+ B cells 10.…”

Section: Introductionmentioning

confidence: 99%

Anti‐TIM‐1 Monoclonal Antibody (RMT1‐10) Attenuates Atherosclerosis By Expanding IgM‐producing B1a Cells

Hosseini

Kanellakis

et al. 2018

JAHA

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BackgroundPeritoneal B1a cells attenuate atherosclerosis by secreting natural polyclonal immunoglobulin M (IgM). Regulatory B cells expressing T‐cell immunoglobulin mucin domain‐1 (TIM‐1) expanded through TIM‐1 ligation by anti‐TIM‐1 monoclonal antibody (RMT1‐10) induces immune tolerance.Methods and ResultsWe examined the capacity of RMT1‐10 to expand peritoneal B1a cells to prevent atherosclerosis development and retard progression of established atherosclerosis. RMT1‐10 treatment selectively doubled peritoneal B1a cells, tripled TIM‐1+ B1a cells and increased TIM‐1+IgM+interleukin (IL)‐10+ by 3‐fold and TIM‐1+IgM+IL‐10− B1a cells by 2.5‐fold. Similar expansion of B1a B cells was observed in spleens. These effects reduced atherosclerotic lesion size, increased plasma IgM and lesion IgM deposits, and decreased oxidatively modified low‐density lipoproteins in lesions. Lesion CD4+ and CD8+ T cells, macrophages and monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, expression of proinflammatory cytokines monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, IL1β, apoptotic cell numbers and necrotic cores were also reduced. RMT1‐10 treatment failed to expand peritoneal B1a cells and reduce atherosclerosis after splenectomy that reduces B1a cells, indicating that these effects are B1a cell‐dependent. Apolipoprotein E‐KO mice fed a high‐fat diet for 6 weeks before treatment with RMT1‐10 also increased TIM‐1+IgM+ IL‐10+ and TIM‐1+IgM+ IL‐10− B1a cells and IgM levels and attenuated progression of established atherosclerosis.Conclusions RMT1‐10 treatment attenuates atherosclerosis development and progression by selectively expanding IgM producing atheroprotective B1a cells. Antibody‐based in vivo expansion of B1a cells could be an attractive approach for treating atherosclerosis.

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Prevention of Arthritis by Interleukin 10–producing B Cells

Cited by 763 publications

References 33 publications

A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells

A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

Anti‐TIM‐1 Monoclonal Antibody (RMT1‐10) Attenuates Atherosclerosis By Expanding IgM‐producing B1a Cells

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