Efficient IgG-mediated suppression of primary antibody responses in Fcγ receptor-deficient mice

Karlsson, Mikael C. I.; Wernersson, Sara; Ståhl, Teresita Díaz de; Gustavsson, Susanne; Heyman, Birgitta

doi:10.1073/pnas.96.5.2244

Cited by 128 publications

(223 citation statements)

References 51 publications

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“…A well-known example of this is the ability of IgG to completely suppress the response to large particulate Ags like erythrocytes (2). The suppressive capacity of IgG is used successfully in the clinic to prevent rhesus D-negative women from becoming immunized against fetal rhesus D-positive erythrocytes transferred via transplacental hemorrhage (3,4).…”

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confidence: 99%

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

Hjelm

Karlsson

Heyman

2008

The Journal of Immunology

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Ag administered i.v. to mice along with specific IgE or IgG2a induces higher Ab- and CD4+ T cell responses than Ag administered alone. The IgE effect is completely dependent on the low-affinity receptor for IgE, CD23, whereas the IgG2a effect depends on activating FcγRs. In vitro studies suggest that IgE/Ag is presented more efficiently than Ag alone to CD4+ T cells by CD23+ B cells and that IgG2a/Ag is presented by FcγR+ dendritic cells (DCs). In this study, we investigate in vivo the early events leading to IgE- and IgG2a-mediated enhancement of immune responses. OVA administered i.v. in PBS in combination with specific IgE binds circulating B cells after 5 min and is found in B cell follicles bound to follicular B cells (CD23high) after 30 min. This novel B cell-dependent route of entry is specific for IgE because IgG2a-Ag complexes were trapped in the marginal zone. OVA-specific CD4+ T cells were found at the T-B border in the T cell zones 12 h after immunization both with IgE/OVA or IgG2a/OVA and proliferated vigorously after 3 days. The findings suggest that IgE- and IgG2a-immune complexes are efficient stimulators of early CD4+ T cell responses and that Ag bound to IgE has a specific route for transportation into follicles.

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confidence: 99%

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

Hjelm

Karlsson

Heyman

2008

The Journal of Immunology

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“…In contrast to these events under normal conditions (see Fig. 1, boxes 1-7), under AMIS conditions, serum IgM and IgG Abs (17), as well as Ag-specific ASC (18,19) are decreased (see Fig. 1, boxes 6 and 7).…”

Section: Transfusion Of Igg-opsonized Foreign Red Blood Cellsmentioning

confidence: 77%

“…Because the APC function of B cells depends on successful priming (24,25), B cell priming is probably either absent, down-regulated, or otherwise changed under AMIS conditions. We and others have observed that immunization at early time points after AMIS induction did not lead to suppression, but rather generated a secondary-like Ab response (19,33,34). This secondary-like response, a priori, excludes B cell anergy, B cell clonal deletion, or B cell clonal silencing as likely mechanisms for the observed lack of Ag-specific B cell APC function in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…In murine models of AMIS, it is clear that T cells are primed against SRBCs following transfusion of IgG-opsonized SRBCs to mice (17)(18)(19), indicating that sufficient Ag processing and presentation to T cells likely occurs under AMIS conditions (see Fig. 1, box 1).…”

Section: Transfusion Of Igg-opsonized Foreign Red Blood Cellsmentioning

confidence: 99%

“…with 10 7 washed SRBCs in PBS (pH 7.22) or with 10 7 SRBCs preincubated for 1 h at 37°C with 10 g of IgG anti-SRBC, without further washing, and both the SRBCs and IgG were injected (19).…”

Section: Immunizationsmentioning

confidence: 99%

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Transfusion of IgG-Opsonized Foreign Red Blood Cells Mediates Reduction of Antigen-Specific B Cell Priming in a Murine Model

Brinc

Le-Tien

Crow

et al. 2008

The Journal of Immunology

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Hemolytic disease of the fetus and newborn can be effectively prevented by administration of anti-D to the mother. The administered IgG results in the attenuation of RBC-specific Ab production, a process termed Ab-mediated immune suppression (AMIS). Because in animal models of AMIS no major effect on T cell priming occurs, we hypothesized that the effect of the IgG on the immune system under AMIS conditions may involve a deficiency in B cell priming. We therefore challenged mice with either untreated RBCs or IgG-opsonized RBCs (AMIS) and assessed B cell priming. B cells from mice transfused with untreated RBCs, but not from mice treated under AMIS conditions, were primed as assessed by their ability to function as Ag-specific APCs to appropriate T cells. To our knowledge, this is the first report demonstrating that AMIS inhibits the appearance of Ag-primed RBC-specific B cells.

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Identification of an Fc? receptor-independent mechanism by which intravenous immunoglobulin ameliorates antiphospholipid antibody-induced thrombogenic phenotype

Pierangeli¹,

Espinola²,

Liu³

et al. 2001

Arthritis & Rheumatism

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Objective Patients with the antiphospholipid antibody syndrome (APS) often experience recurrent arterial and venous thrombosis and pregnancy losses. Intravenous immunoglobulin (IVIG) therapy has prevented pregnancy loss in some women with APS and has reversed fetal resorption rates in murine models of pregnancy loss. Although the basis for these effects is unknown, effector mechanisms of pathogenic antibodies often involve receptors for IgG (Fcγ receptors [FcγR]). We examined the potential mechanisms of action of IVIG in an in vivo murine model of antiphospholipid antibody (aPL)–induced thrombosis and endothelial cell activation. Methods Mice infused with IgG containing human anticardiolipin antibodies (aCL) were treated with IVIG (36 μg IV), saline, or ovalbumin. Surgically induced thrombus formation and in vivo leukocyte adhesion to endothelial cells were measured. Circulating levels of aCL were measured by enzyme‐linked immunosorbent assay. To determine whether FcγR are required for the effects of IVIG, we treated mice deficient in stimulatory FcγR. To examine the effects of IVIG on endogenously generated antibody, we treated mice immunized with β2‐glycoprotein I (β2GPI). Results IVIG treatment inhibited aPL‐induced endothelial cell activation and enhancement of thrombosis in mice passively infused with human aPL–containing IgG, and this was associated with a decrease in aPL levels. Similarly, IVIG lowered aPL levels and inhibited thrombogenesis in mice immunized with β2GPI. The thrombophilic effects of aPL were evident in FcγR‐deficient mice. Conclusion Treatment with IVIG inhibits the thrombogenic effects of aPL in vivo and reduces the levels of aCL in the circulation. Blockade of stimulatory FcγR on inflammatory cells is not necessary for this effect. The mechanism of action of IVIG is more likely saturation of the IgG transport receptor, leading to accelerated catabolism of pathogenic aPL. These results have implications in the management of thrombosis in APS and may have applications for pregnant patients with a history of APS.

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Efficient IgG-mediated suppression of primary antibody responses in Fcγ receptor-deficient mice

Cited by 128 publications

References 51 publications

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

Transfusion of IgG-Opsonized Foreign Red Blood Cells Mediates Reduction of Antigen-Specific B Cell Priming in a Murine Model

Identification of an Fc? receptor-independent mechanism by which intravenous immunoglobulin ameliorates antiphospholipid antibody-induced thrombogenic phenotype

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