B cell activating factor (BAFF) induces the transcription of recombination-activating genes in transitional stage 1 B cells

He, Youdi; Ma, Ning; Xiao, He; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yán; Wang, Renxi; Hu, W. Z.

doi:10.5114/ceji.2013.37758

Cited by 2 publications

(2 citation statements)

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“…BAFF, a proinflammatory cytokine that belongs to the TNF superfamily, has recently emerged as a key regulator in B cell development and function (33). Loss of BAFF impairs B cell development at the transitional stage from T1 B to T2 B cells, thereby decreasing the number of mature B cells and hence Ig level and autoantibodies (34). The expression of BAFF is elevated in patients with autoimmune diseases such as rheumatic arthritis, multiple sclerosis, SLE, and asthma, and belimumab, which is known as a mAb targeting human BAFF, has become the first approved targeted therapy for SLE (35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

Deng

Bian

et al. 2017

The Journal of Immunology

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The genetic association of orosomucoid-like 3 (ORMDL3) with an array of immunoinflammatory disorders has been recently unraveled in multiple ethnic groups, and functional exploration has received attention of the particular relevance of this gene in endoplasmic reticulum stress, lipid metabolism, and inflammatory response. In this study, we demonstrated the upregulation of ORMDL3 in both patients with systemic lupus erythematosus and lupus mice compared with controls. By establishing ORMDL3 knockout mice (), we showed that silencing Ormdl3 in vivo significantly decreased the proportions of mature B lymphocytes and transitional 2B cells in spleen and B1a cells from abdominal cavity perfusion fluid, the secretion of IgG and IgM, and the expression of Baff. Additionally, knockdown of Ormdl3 augmented the apoptosis of total splenic cells and splenic CD19 B cells but did not affect B cell proliferation and cell cycle. Subsequently, we in vitro and in vivo demonstrated that ORMDL3 potentially mediates the autophagy via the ATF 6-Beclin1 autophagy pathway, and it facilitates the survival of splenic B cells via promoting autophagy and suppressing apoptosis. Taken together, we uncovered a role of ORMDL3 in fine-tuning B cell development and survival, besides highlighting a potential mechanism by which ORMDL3 regulates autophagy via ATF6 pathway.

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Section: Discussionmentioning

confidence: 99%

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

Deng

Bian

et al. 2017

The Journal of Immunology

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“…Therefore, IgG4-RD includes a wide variety of diseases, including autoimmune pancreatitis, Mikulicz's disease, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudotumor [ 6 , 7 ]. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production [ 8 , 9 ]. The aim of this study was to investigate the contribution of serum trypsin and TCR in the pathogenesis of IgG4-RD.…”

Section: Introductionmentioning

confidence: 99%

Clinical immunology Serum trypsin and TCR as novel markers for predicting disease activity in IgG4-related disease

Wang¹,

Yi²,

Gao³

et al. 2014

cejoi

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BackgroundIgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD.Material and methodsA prospective cohort study of 22 patients with IgG4-RD was carried out from May 2009 to December 2012, and 65 cases with acute pancreatitis, 60 cases with pancreatic cancer and 120 healthy individuals were studied as controls. Serum TCR, trypsin and IgG4 levels were measured during pre- and post-treatment in the patients with IgG4-RD and their correlations with IgG4 were also assessed.ResultsSerum IgG4 and IgE levels in all patients were significantly increased, and tumor markers (carbohydrate antigen 19-9 and/or carbohydrate antigen 125) were also increased (12/22). Serum trypsin in patients with IgG4-RD was lower than in the ones with acute pancreatitis, pancreatic cancer, and healthy individuals. But serum TCR of IgG4-RD was significantly higher than in the pancreatic cancer group and normal controls and it was inversely correlated with the levels of IgG4 (r = –3.160, p = 0.042).ConclusionsThe results indicate that serum TCR and trypsin might be useful markers for predicting disease activity in IgG4-RD.

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B cell activating factor (BAFF) induces the transcription of recombination-activating genes in transitional stage 1 B cells

Abstract: Abstract

Cited by 2 publications

References 23 publications

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

Clinical immunology Serum trypsin and TCR as novel markers for predicting disease activity in IgG4-related disease

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