Altered Expression of Fcγ and Complement Receptors on B Cells in Systemic Lupus Erythematosus

Gergely, P; Isaák, Andrea; Szekeres, Zsuzsanna; Prechl, József; Erdei, Anna; Nagy, Zsolt B.; Gergely, J.; Poór, Gyula

doi:10.1196/annals.1422.020

Cited by 10 publications

(7 citation statements)

References 47 publications

(45 reference statements)

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“…FcγR regulates autoantibody and IC-induced inflammation. FcγRIIB is expressed on B-cells, mast cells, dendritic cells, neutrophils, macrophages, and osteoclasts 9,16 . Decreased expression of FcγRIIB on germinal center B-cells was associated with strain-specific susceptibility to autoimmune disease.…”

Section: Discussionmentioning

confidence: 99%

Lupus-like Disease in FcγRIIB−/− Mice Induces Osteopenia

Visitchanakun

Saiworn

Jongwattanapisan

et al. 2019

Sci Rep

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Osteoporotic fracture is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Mice lacking Fc gamma receptor IIb (FcγRIIB) spontaneously develop lupus-like disease or SLE at 6-month-old. The aim of this study was to investigate whether FcγRIIB deletion induces osteopenia. μCT analysis indicated that deleting FcγRIIB did not affect cancellous bone microarchitecture in 3-month-old mice in which SLE had not yet developed. However, 6- and 10-month-old FcγRIIB−/− males that developed an SLE-like phenotype were osteopenic and FcγRIIB deletion resulted in decreased cancellous bone volume. Histomorphometry confirmed a significant decrease in cancellous bone volume in 6- and 10-month-old FcγRIIB−/− males. The osteoclast number was increased without any change in osteoblast number. In vitro assays indicated that deleting FcγRIIB increased osteoclast differentiation while alkaline phosphatase activity and mineralization were unaltered. These changes were associated with increases in steady-state mRNA levels for the osteoclast marker genes Trap and Ctsk. Moreover, FcγRIIB−/− mice had higher level of serum TNFα, a proinflammatory cytokine. A soluble TNFα receptor, etanercept, prevented cancellous bone loss in FcγRIIB−/− mice. Our results indicate that FcγRIIB indirectly regulates cancellous bone homeostasis following SLE development. FcγRIIB deletion induces inflammatory bone loss due to increased TNFα-mediated bone resorption without any change in bone formation in mice with SLE-like syndrome.

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Section: Discussionmentioning

confidence: 99%

Lupus-like Disease in FcγRIIB−/− Mice Induces Osteopenia

Visitchanakun

Saiworn

Jongwattanapisan

et al. 2019

Sci Rep

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“…Although FcγRs are clearly implicated in the development of lupus in genetic studies of gain-of-function and loss-of-function mutations and copy numbers of FcγR genes, their role in predisposition to lupus nephritis and/or tissue injury is not as clear [29-32]. In mice, knockout of specific FcγR can lead to accentuation or diminution of disease; most of the effect, however, is on development of lupus rather than specific tissue injury [33,34]. Any impact of FcγR on disease is highly dependent on background strain [35].…”

Section: Fcγ Receptors and Toll-like Receptors In Lupus Nephritismentioning

confidence: 99%

Mechanisms of tissue injury in lupus nephritis

2011

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Systemic lupus erythematosus is a prototypic autoimmune disease characterized by autoantibody production and immune complex formation/deposition in target organs such as the kidney. Resultant local inflammation then leads to organ damage. Nephritis, a major cause of morbidity and mortality in patients with lupus, occurs in approximately 50% of lupus patients. In the present review, we provide an overview of the current research and knowledge concerning mechanisms of renal injury in both lupus-prone mouse models and human lupus patients.

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“…One of the targets of Lyn, the immunoglobulin binding receptor FcγRIIB is a strong candidate for genetic differences that might account for intrinsic changes in SLE B cell signaling [22]. FcγRIIB contains an ITIM that upon phosphorylation recruits SH2 containing inositol phosphate phosphatase which destabilizes and down regulates the BCR signaling complex [23].…”

Section: Impaired Fcγriib Expressions and Activity In Slementioning

confidence: 99%

Altered B cell receptor signaling in human systemic lupus erythematosus

Jenks

Sanz

2009

Autoimmunity Reviews

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Regulation of B cell receptor signaling is essential for the development of specific immunity while retaining tolerance to self. Systemic lupus erythematosus (SLE) is characterized by a loss of B cell tolerance and the production of anti-self antibodies. Accompanying this break down in tolerance are alterations in B cell receptor signal transduction including elevated induced calcium responses and increased protein phosphorylation. Specific pathways that negatively regulate B cell signaling have been shown to be impaired in some SLE patients. These patients have reduced levels of the kinase Lyn in lipid raft microdomains and this reduction is inversely correlated with increased CD45 in lipid rafts. Function and expression of the inhibitory immunoglobulin receptor FcγRIIB is also reduced in Lupus IgM-CD27+ memory cells. Because the relative contribution of different memory and transitional B cell subsets can be abnormal in SLE patients, we believe studies targeted to well defined B cell subsets will be necessary to further our understanding of signaling abnormalities in SLE. Intracellular flow cytometric analysis of signaling is a useful approach to accomplish this goal. • The lipid raft localization of signaling molecules is altered in some SLE patients.Lyn is decreased in lipid rafts and CD45 increased.• Expression and function of the inhibitory immunoglobulin receptor FcγRIIB is reduced in memory B cells in SLE patients.• The composition of memory B cell subsets is altered in SLE patients and they have a higher prevalence of activated cells. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. • B cell signaling in well defined memory subsets can be studied using intracellular flow cytometric analysis. NIH Public Access

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Altered Expression of Fcγ and Complement Receptors on B Cells in Systemic Lupus Erythematosus

Cited by 10 publications

References 47 publications

Lupus-like Disease in FcγRIIB−/− Mice Induces Osteopenia

Lupus-like Disease in FcγRIIB−/− Mice Induces Osteopenia

Mechanisms of tissue injury in lupus nephritis

Altered B cell receptor signaling in human systemic lupus erythematosus

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