Characterization of a rare IL-10–competent B-cell subset in humans that parallels mouse regulatory B10 cells

Iwata, Y.; Matsushita, T.; Horikawa, Mayuka; DiLillo, David J.; Yanaba, Koichi; Venturi, Guglielmo M.; Szabolcs, Paul; Bernstein, Steven H.; Magro, Cynthia M.; Williams, Armistead D.; Hall, Russell P.; Clair, E. William St.; Tedder, Thomas F.

doi:10.1182/blood-2010-07-294249

Cited by 954 publications

(1,258 citation statements)

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“…Interestingly, BCR ligation augmented human B cell IL-10 responses to CpG in one study [49]. This finding is in discordance with our findings in both humans [48] and mice [37], where BCR-generated signals inhibit the abilities of LPS or CpG and CD40 ligation to induce cytoplasmic IL-10 production. Whether human B10 cells develop into antibody-secreting cells or enter the memory pool (memory B10 cells, B10 M ) remains to be determined.…”

Section: Biology Of B10 Cellscontrasting

confidence: 79%

“…B10 PRO cells and B10 cells have been recently identified in humans [48] and their responses to LPS, CpG and CD40 ligation appear to follow the general scheme of mouse B10 cell development (Figure 1). One notable difference in mouse versus human B10 cell development is the lack of response of mouse B10 PRO cells to CpG compared with their human counterparts.…”

Section: Biology Of B10 Cellsmentioning

confidence: 93%

“…The IL-10-producing B cell subset characterized in humans normally represents <1% of peripheral blood B cells [48]. Peripheral blood B10 cells and B10 PRO cells are highly enriched in the CD24 hi CD27 + B cell subset, with approximately 60% also expressing CD38.…”

Section: Biology Of B10 Cellsmentioning

confidence: 99%

“…A separate study showed that B10 cells did not fall within any of the previously defined B cell subsets, but they were enriched in the CD27 + and the CD38 hi compartments [49]. Human B10 cells also highly express CD48 and CD148 [48]. CD48 is a B cell activation marker [52] and CD148 is considered a marker for human memory B cells [53].…”

Section: Biology Of B10 Cellsmentioning

confidence: 99%

“…The CD24 hi CD148 + phenotype of B10 cells and B10 PRO cells may thereby indicate their selection into the memory B cell pool during development, or they may represent a distinct B cell subset that shares common cell surface markers with memory B cells. Consistent with a memory phenotype, the proliferative capacity of human blood B10 cells in response to mitogen stimulation is higher than that for other B cells [48], as is seen for mouse B10 cells [37]. Human transitional B cells are rare (2 to 3% of B cells) in adult human blood and are generally CD10 + CD24 hi CD38 hi cells that are also CD27-negative [55,56]; since CD10 expression is a well-accepted marker for most cells within the transitional B cell pool [57], its absence on B10 cells suggests that these cells are not recent emigrants from the bone marrow.…”

Section: Biology Of B10 Cellsmentioning

confidence: 99%

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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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Section: Biology Of B10 Cellscontrasting

confidence: 79%

Section: Biology Of B10 Cellsmentioning

confidence: 93%

Section: Biology Of B10 Cellsmentioning

confidence: 99%

Section: Biology Of B10 Cellsmentioning

confidence: 99%

Section: Biology Of B10 Cellsmentioning

confidence: 99%

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

2013

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Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjögren Syndrome

Chen

Miao

et al. 2022

JAMA Netw Open

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ImportancePrimary Sjögren syndrome (pSS) is a systemic autoimmune disease associated with dysregulated immune cells, with no efficient therapy. There is a need to study potential therapeutic approaches.ObjectiveTo investigate the efficacy, safety, and immune response of low-dose interleukin 2 (LD-IL-2) in the treatment of pSS.Design, Setting, and ParticipantsA double-blind, placebo-controlled randomized clinical trial was conducted with a 2-group superiority design from June 2015 to August 2017. Sixty patients, aged 18 to 70 years, were recruited from Peking University People’s Hospital. Efficacy analyses were based on the intention-to-treat (ITT) principle. Data were analyzed from December 2018 to March 2020.InterventionsPatients with pSS were treated with LD-IL-2 or placebo for 12 weeks and accompanied by 12 weeks of follow-up.Main Outcomes and MeasuresThe primary end point was defined as a 3-point or greater improvement on the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ESSDAI) by week 24. The secondary end points included other clinical responses, safety, and changes of immune cell subsets at week 12 and 24.ResultsSixty patients with pSS were recruited, with 30 in the LD-IL-2 group (mean [SD] age, 47.6 [12.8] years; 30 [100%] women) and 30 in the placebo group (mean [SD] age, 51.0 [11.9] years; 30 [100%] women), and 57 completed the trial. More patients in the LD-IL-2 group (20 [66.7%]) achieved ESSDAI score reduction of at least 3 points than in the placebo group (8 [26.7%]) at week 24 (P = .004). There were greater resolutions of dryness, pain, and fatigue in the LD-IL-2 group than placebo group at week 12 (dryness: difference, −18.33 points; 95% CI, −28.46 to −8.21 points; P = .001; pain: difference, −10.33 points; 95% CI, −19.38 to −1.29 points; P = .03; fatigue: difference, −11.67 points; 95% CI, −20.65 to −2.68 points; P = .01). No severe adverse events were observed in either group. In addition, the LD-IL-2 group showed a significant decrease in infection compared with the placebo group (1 [3.3%] vs 9 [30.0%]; P = .006). Immunological analysis revealed that LD-IL-2 promoted an expansion of regulatory T cells and regulatory CD24highCD27+ B cells.Conclusions and RelevanceIn this randomized clinical trial, LD-IL-2 was effective and well tolerated in patients with pSS, and it restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells.Trial RegistrationClinicalTrials.gov Identifier: NCT02464319

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The Effect of Glatiramer Acetate Therapy on Functional Properties of B Cells From Patients With Relapsing-Remitting Multiple Sclerosis

et al. 2014

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IMPORTANCEThis study describes what is, to our knowledge, the previously unknown effect of glatiramer acetate therapy on B cells in patients with relapsing-remitting multiple sclerosis (MS).OBJECTIVE To determine whether glatiramer acetate therapy normalizes dysregulated B-cell proliferation and cytokine production in patients with MS. DESIGN, SETTING, AND PARTICIPANTS Twenty-two patients with MS who were receiving glatiramer acetate therapy and 22 treatment-naive patients with MS were recruited at The University of Texas Southwestern Medical Center MS clinic. Cell samples from healthy donors were obtained from HemaCare (Van Nuys, California) or Carter Blood Bank (Dallas, Texas). Treatment-naive patients with MS had not received any disease-modifying therapies for at least 3 months before the study.EXPOSURES Glatiramer acetate therapy for at least 3 months at the time of the study. MAIN OUTCOMES AND MEASURES B-cell phenotype and proliferation and immunoglobulin and cytokine secretion.RESULTS A restoration of interleukin 10 production by peripheral B cells was observed in patients undergoing glatiramer acetate therapy as well as a significant reduction of interleukin 6 production in a subset of patients who received therapy for less than 32 months. Furthermore, proliferation in response to high-dose CD40L was altered and immunoglobulin production was elevated in in vitro-activated B cells obtained from patients who received glatiramer acetate.CONCLUSIONS AND RELEVANCE Glatiramer acetate therapy remodels the composition of the B-cell compartment and influences cytokine secretion and immunoglobulin production. These data suggest that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS that may contribute to the therapeutic mechanisms of glatiramer acetate.

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Characterization of a rare IL-10–competent B-cell subset in humans that parallels mouse regulatory B10 cells

Cited by 954 publications

References 50 publications

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

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

Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjögren Syndrome

The Effect of Glatiramer Acetate Therapy on Functional Properties of B Cells From Patients With Relapsing-Remitting Multiple Sclerosis

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