ORCID Profile
0000-0002-0932-5026
Current Organisation
Monash University
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Publisher: Wiley
Date: 16-07-2020
DOI: 10.1111/SJI.12921
Publisher: Springer Science and Business Media LLC
Date: 16-10-2018
DOI: 10.1038/S41598-018-33087-6
Abstract: Specific IgG antibodies, passively administered together with erythrocytes, suppress antibody responses against the erythrocytes. Although used to prevent alloimmunization in Rhesus (Rh)D-negative women carrying RhD-positive fetuses, the mechanism behind is not understood. In mice, IgG suppresses efficiently in the absence of Fcγ-receptors and complement, suggesting an Fc-independent mechanism. In line with this, suppression is frequently restricted to the epitopes to which IgG binds. However, suppression of responses against epitopes not recognized by IgG has also been observed thus arguing against Fc-independence. Here, we explored the possibility that non-epitope specific suppression can be explained by steric hindrance when the suppressive IgG binds to an epitope present at high density. Mice were transfused with IgG anti-4-hydroxy-3-nitrophenylacetyl (NP) together with NP-conjugated sheep red blood cells (SRBC) with high, intermediate, or low NP-density. Antibody titers and the number of single antibody-forming cells were determined. As a rule, IgG suppressed NP- but not SRBC-specific responses (epitope specific suppression). However, there was one exception: suppression of both IgM anti-SRBC and IgM anti-NP responses occurred when high density SRBC-NP was administered (non-epitope specific suppression). These findings answer a longstanding question in antibody feedback regulation and are compatible with the hypothesis that epitope masking explains IgG-mediated immune suppression.
Publisher: Wiley
Date: 23-12-2014
DOI: 10.1111/SJI.12248
Abstract: IgE-antigen complexes, administered intravenously to mice, induce a several 100-fold higher specific antibody response than antigen alone. Additionally, in vivo activation and proliferation of specific CD4(+) T cells is enhanced. The mechanism behind these effects is thought to be that peripheral B cells capture IgE-antigen complexes via their low-affinity receptor for IgE, CD23, and rapidly transport them to splenic B cell follicles where an immune response is initiated. Here, we demonstrate that ovalbumin, covalently coupled to anti-CD23 antibodies and administered intravenously to mice, is also transported to splenic follicles and induces an enhanced primary antibody response. These effects are absent in CD23-deficient mice. No enhanced induction of immunological memory was observed. These findings extend previous observations regarding the in vivo role of CD23 and emphasize that recirculating B cells play an important role in antigen transport to the spleen.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.JHEP.2021.07.031
Abstract: HBsAg-specific antibody responses are difficult to detect during chronic hepatitis B infection (CHB) and are often overlooked. The aim of this study was to examine whether anti-HBs may be involved in functional cure (FC) by profiling anti-HBs responses in patients with CHB using a panel of specific assays. Longitudinal serum s les were obtained from 25 patients with CHB who were infected with HBV genotype A and were undergoing nucleos(t)ide analogue (NA) treatment: 14 achieved FC while 11 remained infected (non-FC). Anti-HBs immune complexes (HBsAg-IC), FcγRIIIa dimer binding, epitope specificity and neutralisation efficacy were measured. HBsAg-IC peaks were detected prior to HBsAg loss in 10/14 FC patients. These HBsAg-IC peaks overlapped with either an alanine aminotransferase (ALT) flare (8/10 patients), or a rise in ALT (2/10 patients). HBsAg-IC peaks were detected in 7/11 non-FC patients, but were not associated with an ALT flare. FCγRIIIa binding was detected in 9/14 FC patients, independent from detection of overlapping HBsAg-IC/ALT peaks. FC patients had stable HBsAg epitope occupancy across the study, whereas non-FC patients had a reduction in HBsAg epitope occupancy within the first 12-24 weeks of NA treatment. Convalescent sera from FC patients recognised more HBsAg epitopes and neutralised HBV infection more potently than anti-HBs derived from vaccinees. Neutralisation potency appeared to increase post-HBsAg loss in 4/5 FC patients examined. Using these assays, we confirm that anti-HBs responses are present and fluctuate over time in this cohort of patients with HBeAg+ CHB, who were infected with HBV genotype A and treated with NAs. Key anti-HBs profiles associated with either FC or failure to achieve FC were also identified, suggesting a role for anti-HBs responses in FC. Using a panel of assays to characterise hepatitis B surface antibody (anti-HBs) responses in a group of patients with chronic hepatitis B, we identified anti-HBs profiles associated with either functional cure, or failure to achieve functional cure. Functional cure was associated with immune complex peaks which overlapped with alanine aminotransferase flares. Conversely, in those who did not achieve functional cure, immune complex peaks were present, but were not associated with alanine aminotransferase flares, and a decline in anti-HBs ersity was observed early during treatment.
Publisher: The American Association of Immunologists
Date: 15-08-2014
Abstract: Ag administered together with specific IgG3 induces a higher Ab response than Ag administered alone, an effect requiring the presence of complement receptors 1 and 2 (CR1/2). In this study, we have investigated the fate of Ag, the development of germinal centers (GCs), and the Ab response after i.v. administration of IgG3 anti-trinitrophenyl (TNP) in complex with OVA-TNP. After 2 h, OVA-TNP was detected on marginal zone (MZ) B cells, and a substantial amount of Ag was detected in splenic follicles and colocalized with follicular dendritic cells (FDCs). After 10 d, the percentage of GCs and the IgG responses were markedly higher than in mice immunized with uncomplexed OVA-TNP. The effects of IgG3 were dependent on CR1/2 known to be expressed on B cells and FDCs. Using bone marrow chimeric mice, we demonstrate that an optimal response to IgG3-Ag complexes requires that CR1/2 is expressed on both cell types. These data suggest that CR1/2+ MZ B cells transport IgG3-Ag-C complexes from the MZ to the follicles, where they are captured by FDCs and induce GCs and IgG production. This pathway for initiating the transport of Ags into splenic follicles complements previously known B-cell dependent pathways where Ag is transported by 1) MZ B cells, binding large Ags-IgM-C complexes via CR1/2 2) recirculating B cells, binding Ag via BCR or 3) recirculating B cells, binding IgE-Ag complexes via the low-affinity receptor for IgE, CD23.
Publisher: Future Medicine Ltd
Date: 05-2020
Abstract: The clinical sequelae associated with chronic HBV infection is generally regarded as a consequence of an inadequate and inappropriate immune response to active viral replication, predominantly at the T-cell level. However, recent studies on hepatitis B surface antigen (HBsAg)-specific B cells and hepatitis B surface antibody (anti-HB) responses have identified their previously unrecognized role in the pathogenesis of chronic hepatitis B (CHB). These studies have also uncovered novel therapeutic approaches to more effectively target HBsAg loss and seroconversion, an important end point and regarded as a functional cure. Anti-HBs IgG has also been shown to have multiple direct acting antiviral roles with the Fab component directly blocking viral entry, and release while the Fc component has been linked to antibody dependent cellular cytotoxicity. Likewise, the HBsAg-specific B-cell dysfunctionality can be reversed providing new therapeutic opportunities to achieve functional cure in CHB.
Publisher: Frontiers Media SA
Date: 06-03-2017
Publisher: Springer Science and Business Media LLC
Date: 16-06-2016
DOI: 10.1038/SREP28290
Abstract: IgE, forming an immune complex with small proteins, can enhance the specific antibody and CD4 + T cell responses in vivo . The effects require the presence of CD23 (Fcε-receptor II) + B cells, which capture IgE-complexed antigens (Ag) in the circulation and transport them to splenic B cell follicles. In addition, also CD11c + cells, which do not express CD23, are required for IgE-mediated enhancement of T cell responses. This suggests that some type of dendritic cell obtains IgE-Ag complexes from B cells and presents antigenic peptides to T cells. To elucidate the nature of this dendritic cell, mice were immunized with ovalbumin (OVA)-specific IgE and OVA and different populations of CD11c + cells, obtained from the spleens four hours after immunization, were tested for their ability to present OVA. CD8α − conventional dendritic cells (cDCs) were much more efficient in inducing specific CD4 + T cell proliferation ex vivo than were CD8α + cDCs or plasmacytoid dendritic cells. Thus, IgE-Ag complexes administered intravenously are rapidly transported to the spleen by recirculating B cells where they are delivered to CD8α − cDCs which induce proliferation of CD4 + T cells.
No related grants have been discovered for Hui Xu.