The protein tyrosine phosphatase PTP1B is a negative regulator of CD40 and BAFF-R signaling and controls B cell autoimmunity

Medgyesi, Dávid; Hobeika, Elias; Biesen, Robert; Kollert, Florian; Taddeo, Adriano; Voll, R.; Hiepe, Falk; Reth, Michael

doi:10.1084/jem.20131196

Cited by 55 publications

(60 citation statements)

References 52 publications

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“…PTP1B has been shown as a regulator of MAPK activation in B cells [20], and PI3K/AKT activation in adipocytes [38]. In contrast, our western blot analysis revealed that these signaling pathways in FceRI-dependent mast cells are not affected by PTP1B deficiency.…”

Section: Discussioncontrasting

confidence: 58%

“…of PTP1B substrates have been identified. These substrates include cell surface receptors such as EGFR [15], insulin receptor (IR) [16] and a range of intracellular signaling molecules such as c-Src [17], STAT5 [18], JAK2 [19], p38 MAPK [20] or the linker for activation of T-cell (LAT) [21]. Interestingly, many of these potential PTP1B substrates such as LAT, STAT5, or p38 MAPK are also expressed in mast cells and have been recognized as contributors to IgE-mediated signaling in mast cells.…”

Section: Introductionmentioning

confidence: 99%

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Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo

Yang

Xie

et al. 2016

Cellular Immunology

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Section: Discussioncontrasting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo

Yang

Xie

et al. 2016

Cellular Immunology

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“…PTP1B, a protein tyrosine phosphatase, and phosphatase and tensin homolog (PTEN), a lipid phosphatase, are also involved in B-cell tolerance as B cell-specific deletion of these genes causes lupus-like disease 56, 88 . SHIP-1 is activated by mono-phosphorylated immuno-receptor tyrosine-based activation motif at Igα/β.…”

Section: Regulation Of Central Tolerance and Clonal Anergy By Apoptosmentioning

confidence: 99%

“…B cell-specific PTP1B deficiency causes augmented B-cell responses to BAFF, CD40 ligation, and lipopolysaccharide but not BCR ligation and induces lupus-like disease with autoantibody production 56 . PTP1B therefore appears to regulate B-cell tolerance as is the case for SHP-1, although PTP1B regulates a signaling pathway distinct from those regulated by SHP-1 ( Figure 2).…”

Section: Regulation Of Central Tolerance and Clonal Anergy By Apoptosmentioning

confidence: 99%

B-cell tolerance and autoimmunity

Tsubata

2017

F1000Res

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Self-reactive B cells are tolerized at various stages of B-cell development and differentiation, including the immature B-cell stage (central tolerance) and the germinal center (GC) B-cell stage, and B-cell tolerance involves various mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells generated by random immunoglobulin variable gene rearrangements are tolerized by central tolerance and anergy in the periphery, and these processes involve apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP-1. Self-reactive B cells generated by somatic mutations during GC reaction are also eliminated. Fas is not directly involved in this process but prevents persistence of GC reaction that allows generation of less stringently regulated B cells, including self-reactive B cells. Defects in self-tolerance preferentially cause lupus-like disease with production of anti-nuclear antibodies, probably due to the presence of a large potential B-cell repertoire reactive to nucleic acids and the presence of nucleic acid-induced activation mechanisms in various immune cells, including B cells and dendritic cells. A feed-forward loop composed of anti-nuclear antibodies produced by B cells and type 1 interferons secreted from nucleic acid-activated dendritic cells plays a crucial role in the development of systemic lupus erythematosus.

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“…The latter is provided by interaction between CD40 in B cells and CD154/CD40L on the surface of activated CD4 + T cells. However, increasing evidences indicated that TLRs activation provides a third signal for B cell activation and is significant to antigen-specific antibody responses [48, 49]. TLR4 expression is very low on human B cells surface but increases after stimulation of BCR, CD40, TLRs, and some other cytokines [50].…”

Section: The Effects Of Tlr4 In Promoting the Proliferation Activmentioning

confidence: 99%

The Role of TLR4 on B Cell Activation and Anti-β2GPI Antibody Production in the Antiphospholipid Syndrome

Cheng

Wang

Zhou

2016

Journal of Immunology Research

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High titer of anti-β 2-glycoprotein I antibodies (anti-β 2GPI Ab) plays a pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused on the pathological mechanism in APS; however, little attention is paid to the immune mechanism of production of anti-β 2GPI antibodies in APS. Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β 2-glycoprotein I (β 2GPI). TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β 2GPI. However, TLR4 provides a third signal for B cell activation and then promotes B cells better receiving signals from both B cell antigen receptor (BCR) and CD40, thus promoting B cell activation, surface molecules expression, anti-β 2GPI Ab production, and cytokines secretion and making B cell functioning like an antigen presenting cell (APC). At the same time, TLR4 also promotes B cells producing antibodies by upregulating the expression of B-cell activating factor (BAFF). In this paper, we aim to review the functions of TLR4 in B cell immune response and antibody production in autoimmune disease APS and try to find a new way for the prevention and treatment of APS.

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The protein tyrosine phosphatase PTP1B is a negative regulator of CD40 and BAFF-R signaling and controls B cell autoimmunity

Abstract: The protein tyrosine phosphatase PTP1B regulates co-receptor signaling on B cells and thus controls B cell autoimmunity.

Cited by 55 publications

References 52 publications

Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo

Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo

B-cell tolerance and autoimmunity

The Role of TLR4 on B Cell Activation and Anti-β2GPI Antibody Production in the Antiphospholipid Syndrome

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