Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance

Ding, Chuan‐Fan; Ma, Yunfeng; Chen, Xingguo; Liu, Min; Cai, Yihua; Hu, Xiaoling; Xiao, Dong; Nath, Swapan K.; Zhang, Huang‐Ge; Ye, Hong; Powell, David W.; Yan, Jun

doi:10.1038/ncomms3813

Cited by 67 publications

(73 citation statements)

References 48 publications

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“…Primary granulocytes and promyelocytic cells in the bone marrow do not express CD11b and mature myeloid cells and neutrophils is consistently high, this feature can be used to distinguish between promyelocytic cells and other myeloid cell populations. CD11b also plays a role in the maintenance of autoreactive B cell tolerance, which is linked to the pathogenesis of systemic lupus erythematosus and adult‐onset Still's disease . In our study, the expression rate of CD11b was 7% in the APL group, which was different from that reported by Dong et al, and was statistically different from the expression rate in other types of AML (35%).…”

Section: Discussioncontrasting

confidence: 99%

The CD9⁺CD11b⁻HLA‐DR⁻ immunophenotype can be used to diagnose acute promyelocytic leukemia

Ren

Zhang

et al. 2018

Int J Lab Hematology

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Objective To investigate the immunophenotypic characteristics of acute promyelocytic leukemia (APL) and explore the sensitivity and specificity of various antibody combinations for the timely and accurate diagnosis APL. Methods A retrospective analysis was performed using morphological, immunological, genetic, and molecular biological data from 92 patients diagnosed with APL and 190 controls diagnosed with non‐APL acute myeloid leukemia. Results For APL diagnosis, the CD9/CD11b/human leukocyte antigen (HLA)‐DR antibody combination had 85% sensitivity and 95% specificity, AUC = 0.85. However, the sensitivity and specificity were 39% and 92%, AUC = 0.65, respectively, for the HLA‐DR/CD34/CD117 combination, and 80% and 80%, AUC = 0.80, respectively for the CD11b/HLA‐DR combination. Significant differences were observed between the different antibody combinations. Conclusions The CD9/CD11b/HLA‐DR antibody combination displays high sensitivity and specificity and can be used to diagnose APL.

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Section: Discussioncontrasting

confidence: 99%

The CD9⁺CD11b⁻HLA‐DR⁻ immunophenotype can be used to diagnose acute promyelocytic leukemia

Ren

Zhang

et al. 2018

Int J Lab Hematology

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“…We thus asked whether STAT3 signaling in B cells is essential for autoAb response. Apoptotic cells are considered to be the major source of autoAgs that can efficiently stimulate B cells (34, 35). We used anti-snRNP Ig Tg mice in which approximately 30% of B cells bind to autoAg snRNP (24).…”

Section: Resultsmentioning

confidence: 99%

STAT3 Signaling in B Cells Is Critical for Germinal Center Maintenance and Contributes to the Pathogenesis of Murine Models of Lupus

Ding

Chen

Dascani

et al. 2016

The Journal of Immunology

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Antibody maturation as well as memory B and plasma cell differentiation occur primarily in the germinal centers (GC). Systemic lupus erythemotosus (SLE) may develop as a result of enhanced GC activity. Previous studies have shown that the dysregulated signal transducer and activator of transcription 3 (STAT3) pathway is linked to lupus pathogenesis. However, the exact role of STAT3 in regulating SLE disease progression has not been fully understood. Here, we demonstrated that the STAT3 signaling in B cells is essential for the GC formation and maintenance as well as antibody response. Increased cell apoptosis and down-regulated Bcl-xL and Mcl-1 anti-apoptotic gene expression were found in the STAT3 deficient GC B cells. The Tfh cell response positively correlated with the GC B cells and was significantly decreased in immunized B cell STAT3-deficient mice. STAT3 deficiency also led to the defect of plasma cell differentiation. Furthermore, STAT3 deficiency in autoreactive B cells resulted in decreased autoantibody production. Results obtained from B-cell STAT3 deficient B6.MRL/lpr mice suggest that STAT3 signaling significantly contributes to the SLE pathogenesis by regulation of the GC reactivity, autoantibody production, and kidney pathology. Our findings provide new insights into the role of STAT3 signaling in the maintenance of the GC formation and GC B cell differentiation and identify STAT3 as a novel target for the treatment of SLE.

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“…Interestingly, activation of CD11b impedes the accumulation of lipid in macrophages and the formation of foam cells in the presence of IL-13 (16). Its negative regulation of the immune response also can be observed in B cells, because CD11b has been shown to inhibit the autoreactive B-cell response in systemic lupus erythematous (17). Importantly, CD11b is found to be involved in regulating body fat deposition (18); however, the effect of CD11b in obesity-induced insulin resistance has not been reported.…”

mentioning

confidence: 97%

CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages

Zheng

Yang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which is believed to predispose obese individuals to insulin resistance. CD11b (integrin αM) is highly expressed on monocytes and macrophages and is critical for their migration and function. We found here that high-fat diet–induced insulin resistance was significantly reduced in CD11b-deficient mice. Interestingly, the recruitment of monocytes to adipose tissue is impaired when CD11b is deficient, although the cellularity of ATMs in CD11b-deficient mice is higher than that in wild-type mice. We further found that the increase in ATMs is caused mainly by their vigorous proliferation in the absence of CD11b. Moreover, the proliferation and alternative activation of ATMs are regulated by the IL-4/STAT6 axis, which is inhibited by CD11b through the activity of phosphatase SHP-1. Thus, CD11b plays a critical role in obesity-induced insulin resistance by limiting the proliferation and alternative activation of ATMs.

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Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance

Cited by 67 publications

References 48 publications

The CD9⁺CD11b⁻HLA‐DR⁻ immunophenotype can be used to diagnose acute promyelocytic leukemia

The CD9⁺CD11b⁻HLA‐DR⁻ immunophenotype can be used to diagnose acute promyelocytic leukemia

STAT3 Signaling in B Cells Is Critical for Germinal Center Maintenance and Contributes to the Pathogenesis of Murine Models of Lupus

CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages

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Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance

Cited by 67 publications

References 48 publications

The CD9+CD11b−HLA‐DR− immunophenotype can be used to diagnose acute promyelocytic leukemia

The CD9+CD11b−HLA‐DR− immunophenotype can be used to diagnose acute promyelocytic leukemia

STAT3 Signaling in B Cells Is Critical for Germinal Center Maintenance and Contributes to the Pathogenesis of Murine Models of Lupus

CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages

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The CD9⁺CD11b⁻HLA‐DR⁻ immunophenotype can be used to diagnose acute promyelocytic leukemia

The CD9⁺CD11b⁻HLA‐DR⁻ immunophenotype can be used to diagnose acute promyelocytic leukemia