Mesenteric B cells centrally inhibit CD4<sup>+</sup>T cell colitis through interaction with regulatory T cell subsets

Wei, Bo; Velázquez, Peter; Turovskaya, Olga; Spricher, Karsten; Aranda, Richard; Kronenberg, Mitchell; Birnbaumer, Lutz; Braun, Jonathan

doi:10.1073/pnas.0409449102

Cited by 166 publications

(135 citation statements)

References 54 publications

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“…In addition, the presence of decreased numbers of memory B cells as a result of impaired splenic function is associated with the development of IBD in humans (70). Cell transfer studies indicate that although both MLN and splenic MZ B cells suppress intestinal inflammation observed in G␣i2 KO mice, the inflammation is much more efficiently suppressed by MLN B cells as compared with splenic MZ B cells (30). During their migration through the MLN, further activation by enteric bacterial products may be necessary for MZ B cells to acquire full Breg function.…”

Section: Activation/differentiation Pathway Of Bregsmentioning

confidence: 98%

“…An attractive new mechanism by which MLN Bregs may suppress intestinal inflammation is suggested by the work of Braun and colleagues (30) in G␣i2 KO mice. The MLN Breg subset characterized by CD19 high expression is involved in intestinal immunoregulation by recruiting novel Treg subsets, CD8 ϩ T cells, and NKT cells (30), both of which have recently been shown to inhibit intestinal inflammation (86 -88).…”

Section: Mechanisms Other Than Cytokine Production By Which B Cells Cmentioning

confidence: 99%

“…This Breg represents the "acquired type" subset that originates from activated follicular B cell population. Since the pathogenesis of IBD involves both acquired and innate immune responses in the gut-associated lymphoid tissues (GALT) to enteric bacterial products (52, 66), Bregs are most likely to develop in the mesenteric lymph nodes (MLN, a component of GALT) in IBD (23,30). Interestingly, the MLN Breg shares phenotypic and functional features with the splenic MZ B cell subset (23, 28 -30); like splenic MZ B cells (28,64,65), the MLN Breg is characterized by a high level of CD1d expression and responsiveness to LPS.…”

Section: Activation/differentiation Pathway Of Bregsmentioning

confidence: 99%

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A Case for Regulatory B Cells

Mizoguchi

Bhan

2006

The Journal of Immunology

516

396

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B cells are typically characterized by their ability to produce Abs, including autoantibodies. However, B cells possess additional immune functions, including the production of cytokines and the ability to function as a secondary APC. As with T cells, the B cell population contains functionally distinct subsets capable of performing both pathogenic and regulatory functions. Recent studies indicate that regulatory B cells develop in several murine models of chronic inflammation, including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalomyelitis. The regulatory function may be directly accomplished by the production of regulatory cytokines IL-10 and TGF-β and/or by the ability of B cells to interact with pathogenic T cells to dampen harmful immune responses. In this review, we make a case for the existence of regulatory B cells and discuss the possible developmental pathways and functional mechanisms of these B cells.

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Section: Activation/differentiation Pathway Of Bregsmentioning

confidence: 98%

Section: Mechanisms Other Than Cytokine Production By Which B Cells Cmentioning

confidence: 99%

Section: Activation/differentiation Pathway Of Bregsmentioning

confidence: 99%

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A Case for Regulatory B Cells

Mizoguchi

Bhan

2006

The Journal of Immunology

516

396

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“…This IL-10-producing B cell subset appears during chronic inflammation in T cell receptor alpha chain-deficient mice and suppresses the progression of intestinal inflammation by downregulating inflammatory cascades associated with IL-1 upregulation and signal transducer and activator of transcription 3 ( stat3 ) activation rather than by altering polarized T H cell responses. The adoptive transfer of these mesenteric lymph node B cells also suppresses inflammatory bowel disease through a mechanism that correlates with an increase in T REG subsets [67]. Oral administration of dextran sulfate sodium solution to mice is widely used as a model of human ulcerative colitis.…”

Section: B10 Cells In Mouse Models Of Autoimmune Diseasementioning

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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“…These B cells were later shown to appear during chronic intestinal inflammation, exhibit upregulated CD1d expression and release IL-10 (Mizoguchi, Mizoguchi et al 2002). Furthermore, adoptive transfer experiments confirmed a protective role of B cells via mechanisms like IL-10 production and induction of regulatory T cells (Bhan, Mizoguchi et al 2000;Mizoguchi, Mizoguchi et al 2002;Wei, Velazquez et al 2005). Several additional studies performed by different groups using various mouse models have confirmed that B cells can regulate UClike intestinal inflammation (Gerth, Lin et al 2004;Hokama, Mizoguchi et al 2004;Su, Guo et al 2004;Sugimoto, Ogawa et al 2007) as well as Crohn's disease-like conditions (Dalwadi, Wei et al 2003;Wei, Velazquez et al 2005;Ostanin, Pavlick et al 2006).…”

Section: Inflammatory Bowel Diseasementioning

confidence: 82%