Expression profiling of persistent polyclonal B-cell lymphocytosis suggests constitutive expression of the AP-1 transcription complex and downregulation of Fas-apoptotic and TGFβ signalling pathways

Lawrie, Charles H.; Shilling, Rebecca A.; Troussard, Xavier; Cattan, Helen; Mossafa, Hossein; Boultwood, Jacqueline; Wainscoat, James S.; Hatton, Chris

doi:10.1038/leu.2008.223

Cited by 8 publications

(5 citation statements)

References 6 publications

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“…NFKBIA , which encodes IκBα and inhibits NF-κB signaling, was induced by TGF-β3. Other negative regulators of B cell activation and survival, including S1PR2 [35], DUSP4 [36], FCRL4 [37], and STK17A [38, 39], were also induced by TGF-β3 (Fig 5B). …”

Section: Resultsmentioning

confidence: 99%

TGF-β3 Inhibits Antibody Production by Human B Cells

et al. 2017

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TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory cytokine in the immune system and has been reported to inhibit B cell function in both mice and humans. Recently, it has been suggested that TGF-β3 may play an important role in the regulation of immune system in mice. Murine CD4+CD25-LAG3+ regulatory T cells suppress B cell function through the production of TGF-β3, and it has been reported that TGF-β3 is therapeutic in a mouse model of systemic lupus erythematosus. The effect of TGF-β3 on human B cells has not been reported, and we herein examined the effect of TGF-β3 on human B cells. TGF-β3 suppressed B cell survival, proliferation, differentiation into plasmablasts, and antibody secretion. Although the suppression of human B cells by TGF-β1 has long been recognized, the precise mechanism for the suppression of B cell function by TGF-β1 remains elusive; therefore, we examined the effect of TGF-β1 and β3 on pathways important in B cell activation and differentiation. TGF-β1 and TGF-β3 inhibited some of the key molecules of the cell cycle, as well as transcription factors important in B cell differentiation into antibody secreting cells such as IRF4, Blimp-1, and XBP1. TGF-β1 and β3 also inhibited B cell receptor signaling. Our results suggest that TGF-β3 modifying therapy might be therapeutic in autoimmune diseases with B cell dysregulation in humans.

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Section: Resultsmentioning

confidence: 99%

TGF-β3 Inhibits Antibody Production by Human B Cells

et al. 2017

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“…It is downregulated in B-cell lymphoma cases such as Burkitt lymphoma and diffuse large B-cell lymphomas relative to non-neoplastic B cells. 39,40 This observation has been confirmed by Lawrie 41 who showed that miR-150 is downregulated in diffuse large B-cell lymphoma cells compared with normal B cells. 42 RT-PCR using RNA obtained from the diagnostic formalin-fixed, paraffin embedded tissue sample also showed that the low-expression levels of certain miRNAs at diagnosis are associated with an increased risk of progression.…”

Section: Identification Of Mirnas Associated With Outcome In Primary mentioning

confidence: 58%

MicroRNAs as prognostic markers in indolent primary cutaneous B-cell lymphoma

et al. 2013

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Indolent primary cutaneous B-cell lymphoma is a group of malignant lymphomas comprising marginal zone B-cell lymphoma and centrofollicular B-cell lymphoma. Relapse rate of these tumors is close to 40%, and identifying those patients who are likely to progress remains a challenge. The aim of this study was to characterize the microRNA (miRNA) expression profile of a series of primary cutaneous B-cell lymphomas and correlate with histological and clinical findings. We studied a series of 68 patients with primary cutaneous B-cell lymphomas (30 cutaneous marginal-zone B-cell lymphomas and 38 primary cutaneous centrofollicular lymphomas). A set of 11 miRNAs associated with the differentiation stage of B cells was quantified by realtime PCR, using RNA extracted from formalin-fixed, paraffin-embedded tissue diagnostic samples. Relevant clinical variables were retrieved in a subset of 57 patients (28 cutaneous marginal zone B-cell lymphomas and 29 primary cutaneous centrofollicular lymphomas). miR-150 was upregulated in cutaneous marginal zone B-cell lymphomas relative to primary cutaneous centrofollicular lymphoma samples (false discovery rate o0.05). miR-155 and miR-150 expression levels were associated with progression-free survival in a univariate Cox regression analysis (Po0.1). After stratification by histological subtype, low-expression levels of miR-155 and miR-150 were both associated with shorter progression-free survival only in primary cutaneous marginal zone B-cell lymphomas cases (log-rank test, Po0.05). In summary, miRNA expression analysis can be used as a tool for diagnosis and outcome prognosis in indolent primary cutaneous B-cell lymphoma.

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“…It is reasonable to speculate that the interaction of genetic predisposition with chronic antigenic stimulation may lead to the development of PPBL. Very recently, whole genome microarray expression analysis was done in 14 PPBL patients, which demonstrated over-expression of AP-1 transcription complex and downregulation of Fas-apoptotic and TGFβ pathway [5]. The polyclonality of the lymphocyte population evidenced by flow cytometry in this disorder is challenged by rare reports of clonal IGHD-IGHJ immunoglobulin rearrangement in patients otherwise meeting diagnostic criteria of PPBL [6,23].…”

Section: Discussionmentioning

confidence: 99%

Histological and immunohistochemical features of the spleen in persistent polyclonal B-cell lymphocytosis closely mimic splenic B-cell lymphoma

Sun

Juskevicius

2012

Diagn Pathol

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Persistent polyclonal B-cell lymphocytosis (PPBL) is rare and intriguing hematological disorder predominantly reported in young to middle- aged smoking women. It is characterized by persistent moderate polyclonal B-cell lymphocytosis with circulating hallmark binucleated lymphocytes and elevated polyclonal serum IgM. Most patients have benign clinical course on long-term follow-up. Some pathologic features of PPBL may resemble malignant lymphoma, including morphology as well as frequent cytogenetic and molecular abnormalities. Significant symptomatic splenomegaly requiring splenectomy is very unusual for this disorder; therefore there is a lack of descriptions of the morphologic features of the spleen in the literature. We present here one of the first detailed descriptions of the morphologic and immunohistochemical features of the spleen from a young female with PPBL who developed massive splenomegaly during 6-year follow up. Splenectomy was performed for symptomatic relief and suspicion of malignant process. The morphological and immunohistochemical features of the spleen closely mimicked involvement by B-cell lymphoma, however there was no monotypic surface light chain restriction seen by flow cytometry and no clonal rearrangement of IgH gene was detected by molecular analysis. Evaluating a splenectomy sample in cases like this may present a diagnostic challenge to pathologists. Therefore, correlation with B cell clonality studies (by flow cytometry and molecular analysis), clinical findings and peripheral blood morphology searching for characteristic binucleated lymphocytes is essential to avoid misdiagnosing this benign process as B-cell lymphoma. We also present here a literature review on pathogenesis of PPBL.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5329558967545656

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Expression profiling of persistent polyclonal B-cell lymphocytosis suggests constitutive expression of the AP-1 transcription complex and downregulation of Fas-apoptotic and TGFβ signalling pathways

Cited by 8 publications

References 6 publications

TGF-β3 Inhibits Antibody Production by Human B Cells

TGF-β3 Inhibits Antibody Production by Human B Cells

MicroRNAs as prognostic markers in indolent primary cutaneous B-cell lymphoma

Histological and immunohistochemical features of the spleen in persistent polyclonal B-cell lymphocytosis closely mimic splenic B-cell lymphoma

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