The effect of activating and inhibiting Fc-receptors on murine mercury-induced autoimmunity

Martinsson, Κjell; Carlsson, Louise; Kleinau, Sandra; Hultman, Per

doi:10.1016/j.jaut.2008.01.002

Cited by 12 publications

(10 citation statements)

References 37 publications

(49 reference statements)

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“…In genetically susceptible mice, mercury exposure has been shown to induce an autoimmune disease characterized by hypergammaglobulinemia, lymphoproliferation and the presence of IgG antinucleolar antibodies. It was shown, using a mouse strain that is deficient for the FcRg-chain or FcgRIII, that Fc-receptors can be important in the determining activation or inhibition of immune responses [78]. Others substances associated with autoimmunity include iodine [79,80], vinyl chloride [81], canavanine [82], organic solvents [83], L-tryptophan [79], anilides [84], vaccines, microbials, and a variety of pollutants including particulate silica [85], airborne particulate pollution, ozone [86], and ultraviolet radiation [87,88].…”

Section: Other Agents and Autoimmunitymentioning

confidence: 99%

Drugs and autoimmunity – A contemporary review and mechanistic approach

Chang

Gershwin

2010

Journal of Autoimmunity

146

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Section: Other Agents and Autoimmunitymentioning

confidence: 99%

Drugs and autoimmunity – A contemporary review and mechanistic approach

Chang

Gershwin

2010

Journal of Autoimmunity

146

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“…While several other studies have demonstrated that pristane or mercury induced lupus is enhanced in the absence of FcγRIIB [55, 56], our study is the first to demonstrate that high affinity DNA-reactive B cells are selectively expanded. In agreement with the studies of Ravetch and Bolland [20], we observed that non-transgenic FcγRIIB -/- BALB/c mice did not develop anti-DNA antibody titers.…”

Section: Discussionmentioning

confidence: 43%

Selective regulation of autoreactive B cells by FcγRIIB

Jeganathan

Kawabata

Kim

et al. 2009

Journal of Autoimmunity

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FcγRIIB is an inhibitory receptor which plays a role in limiting B cell and DC activation. Since FcγRIIB is known to dampen the signaling strength of the BCR, we wished to determine the impact of FcγRIIB on the regulation of BCRs which differ in their affinity for DNA. For these studies, FcγRIIB deficient BALB/c mice were bred with mice expressing the transgene-encoded H chain of the R4A anti-DNA antibody which gives rise to BCRs which express high, low or no affinity for DNA. The deletion of FcγRIIB in R4A BALB/c mice led to an alteration in the B cell repertoire, allowing for the expansion and activation of high affinity DNA-reactive B cells. By 6 to 8 months of age, R4A × FcγRIIB -/-BALB/c mice spontaneously developed anti-DNA antibody titers. These mice also displayed an induction of IFN-inducible genes and an elevation in levels of the B cell survival factor, BAFF. These data demonstrate that FcγRIIB preferentially limits activation of high affinity autoreactive B cells and can influence the activation of DC through an immune complexmediated mechanism.

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“…FcRγ −/− mice did not respond with a rise of serum IgG1 following Hg treatment as seen in wt mice [27], [28] indicating another mechanism for the elevation of CIC levels. The higher and also more variable CIC levels in the Hg-treated FcRγ −/− mice might be due both to the reduced ability by these mice to handle normal levels of CIC and to the extensive Hg-induced IC-production.…”

Section: Discussionmentioning

confidence: 89%

“…We have previously used FcγR-deficient mice to explore the role of these receptors in HgIA [27], [28], a model characterized by Hg-induced lymphoproliferation, hypergammaglobulinaemia, antinucleolar autoantibodies (ANoA) and IC deposits in the renal glomerular mesangium and systemically in vessel walls in susceptible mouse strains [29]. In HgIA, activating FcγRs affect development of ANoA [28] as well as IC deposits [27], while the inhibiting FcγRIIb down-regulates the hyper-gammaglobulinaemic response [27], [28].…”

Section: Introductionmentioning

confidence: 99%

Deficiency of Activating Fcγ-Receptors Reduces Hepatic Clearance and Deposition of IC and Increases CIC Levels in Mercury-Induced Autoimmunity

et al. 2010

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BackgroundInorganic mercury (Hg) induces a T-cell dependent, systemic autoimmune condition (HgIA) where activating Fcγ-receptors (FcγRs) are important for the induction. In this study we examined the influence of activating FcγRs on circulating levels and organ localization of immune complexes (IC) in HgIA.Methods and Principal FindingsMercury treated BALB/c wt mice showed a significant but modest increase of circulating IC (CIC) from day 12 until day 18 and day 35 for IgG2a- and IgG1- CIC, respectively. Mercury-treated mice lacking the trans-membrane γ-chain of activating FcγRs (FcRγ−/−) had significantly higher CIC levels of both IgG1-CIC and IgG2a-CIC than wt mice during the treatment course. The hepatic uptake of preformed CIC was significantly more efficient in wt mice compared to FcγR−/− mice, but also development of extrahepatic tissue IC deposits was delayed in FcRγ−/− mice. After 35 days of Hg treatment the proportion of immune deposits, as well as the amounts was significantly reduced in vessel FcRγ−/− mice compared to wt mice.ConclusionsWe conclude that mice lacking functional activating FcγRs respond to Hg with increased levels and altered quality of CIC compared with wt mice. Lack of functional activating FcγRs delayed the elimination of CIC, but also significantly reduced extrahepatic tissue localization of CIC.

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The effect of activating and inhibiting Fc-receptors on murine mercury-induced autoimmunity

Cited by 12 publications

References 37 publications

Drugs and autoimmunity – A contemporary review and mechanistic approach

Drugs and autoimmunity – A contemporary review and mechanistic approach

Selective regulation of autoreactive B cells by FcγRIIB

Deficiency of Activating Fcγ-Receptors Reduces Hepatic Clearance and Deposition of IC and Increases CIC Levels in Mercury-Induced Autoimmunity

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