Clearance of anti-double-stranded DNA antibodies: The natural immune complex clearance mechanism

Craig, Maria; Bankovich, Alexander J.; McElhenny, Jennifer L.; Taylor, Ronald P.

doi:10.1002/1529-0131(200010)43:10<2265::aid-anr14>3.0.co;2-j

Cited by 31 publications

(27 citation statements)

References 60 publications

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“…Indeed, we observed that the furin inhibitor CMK and the metalloprotease inhibitor 1,10-phenanthroline demonstrated only marginal inhibition of FcγR induced BLyS/BAFF shedding (results not shown). Interestingly, a similar protease-resistant FcγRI induced cleavage of CR1 (CD35) has been observed (40)(41)(42).…”

Section: Discussionsupporting

confidence: 55%

Immune Opsonins Modulate BLyS/BAFF Release in a Receptor-specific Fashion

Li¹,

Edberg²,

Su³

et al. 2007

Clinical Immunology

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TNF ligand superfamily member 13B (B-lymphocyte stimulator (BLyS), B cell activating factor (BAFF)) promotes primary B cell proliferation and immunoglobulin production. While the soluble form of BLyS/BAFF is thought to be the primary biologically active form, little is known about the regulation of its cleavage and processing. We provide evidence that Fcγ receptor cross-linking triggers a rapid release of soluble, biologically active BLyS/BAFF from myeloid cells. Surprisingly, this function is primarily mediated by FcγRI, but not FcγRIIa as defined by specific mAb, and can be initiated by both IgG and C reactive protein (CRP) as ligands. The generation of a B cell proliferation and survival factor by both innate and adaptive immune opsonins through engagement of an Fcγ receptor, which can also enhance antigen uptake and presentation, provides a unique opportunity to facilitate antibody production. These results provide a mechanism by which Fcγ receptors can elevate circulating BLyS levels and promote autoantibody production in immune complex mediated autoimmune diseases.

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Section: Discussionsupporting

confidence: 55%

Immune Opsonins Modulate BLyS/BAFF Release in a Receptor-specific Fashion

Li¹,

Edberg²,

Su³

et al. 2007

Clinical Immunology

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“…Whether the localized mAb 7G6 is held on FDC by Fc␥R (30,31), or in part by FDCassociated CR1/2, or by CD23, which binds CR2 in primates (59,60), is not revealed presently, but this question may be addressed in appropriate knockout animals. Support for proteolytic release of extracellular B cell CR1/2 is also found in studies that indicated cleavage of a structurally related protein, primate E CR1, is required for the transfer of CR1-bound IC from E to acceptor cells (61)(62)(63). In fact, in diseases associated with C activation and IC processing, levels of both E CR1 and B cell CR2 are reduced substantially (47, 64 -66).…”

Section: Transfer To Fdcs Appears To Be Mediated By Extracellular Promentioning

confidence: 84%

Analyses of the In Vivo Trafficking of Stoichiometric Doses of an Anti-Complement Receptor 1/2 Monoclonal Antibody Infused Intravenously in Mice

Whipple

Shanahan

Ditto

et al. 2004

The Journal of Immunology

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Complement plays a critical role in the immune response by opsonizing immune complexes (IC) and thymus-independent type 2 Ags with C3 breakdown product C3dg, a CR2-specific ligand. We used a C3dg-opsonized IC model, anti-CR1/2 mAb 7G6, to investigate how such substrates are processed. We used RIA, whole body imaging, flow cytometry, and fluorescence immunohistochemistry to examine the disposition of 0.1- to 2-μg quantities of mAb 7G6 infused i.v. into BALB/c mice. The mAb is rapidly taken up by the spleen and binds preferentially to marginal zone (MZ) B cells; within 24 h, the MZ B cells relocate and transfer mAb 7G6 to follicular dendritic cells (FDC). Transfer occurs coincident with loss of the extracellular portion of MZ B cell CR2, suggesting that the process may be mediated by proteolysis of CR2. Intravenous infusion of an FDC-specific mAb does not induce comparable splenic localization or cellular reorganization, emphasizing the importance of MZ B cells in intrasplenic trafficking of bound substrates. We propose the following mechanism: binding of C3dg-opsonized IC to noncognate MZ B cells promotes migration of these cells to the white pulp, followed by CR2 proteolysis, which allows transfer of the opsonized IC to FDC, thus facilitating presentation of intact Ags to cognate B cells.

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“…The transfer mechanism could be driven by a higher number of CR1 copies on the monocyte than on the RBCs (63) or by the close juxtaposition of the macrophage to the RBC-bound ICs that leads to macrophageassociated protease cleavage of CR1 and a release of the IC from the RBC (64). It is possible that instability of RBC membranes may occur during transfer of CR1-bound ICs from erythrocytes to acceptor phagocytic cells via Fc receptors (64,65) and thus trigger RBCs to shed MPs.…”

Section: Cd235mentioning

confidence: 99%

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

Punyadee

Mairiang

Thiemmeca

et al. 2015

J Virol

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Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1-anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. IMPORTANCEDengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed cell death and MP release. In patients' blood, the majority of MPs originated from red blood cells and platelets. Decreased platelet-derived MPs were associated with a bleeding tendency, while increased levels of red blood cell-derived MPs (RMPs) correlated with more severe disease. Importantly, the level of RMPs during the early acute phase could serve as a biomarker to identify patients with potentially severe disease who require immediate care. E ach year, up to 390 million people are infected by dengue virus (DENV), the most significant mosquito-borne virus of the Flaviviridae family, posing serious socioeconomic and health burdens globally (1). Four serotypes of viruses (DENV serotype 1 [DENV-1], DENV-2, DENV-3, and DENV-4) are transmitted to humans by Aedes mosquitoes to establish both endemic and epidemic transmission cycles primarily in tropical and subtropical countries (1). Although the majority of DENV infections in humans are subclinical, a small fraction of infected individuals develops clinical symptoms ranging from a self-...

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Clearance of anti-double-stranded DNA antibodies: The natural immune complex clearance mechanism

Cited by 31 publications

References 60 publications

Immune Opsonins Modulate BLyS/BAFF Release in a Receptor-specific Fashion

Immune Opsonins Modulate BLyS/BAFF Release in a Receptor-specific Fashion

Analyses of the In Vivo Trafficking of Stoichiometric Doses of an Anti-Complement Receptor 1/2 Monoclonal Antibody Infused Intravenously in Mice

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

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