ORCID Profile
0000-0002-7585-7848
Current Organisation
Westmead Institute for Medical Research
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Publisher: Elsevier BV
Date: 03-2020
Publisher: Tsinghua University Press
Date: 06-2020
Publisher: Elsevier BV
Date: 05-2020
Publisher: Wiley
Date: 26-09-2019
DOI: 10.1111/IMR.12808
Abstract: The adaptive immune system is tasked with producing antibodies that recognize a wide scope of potential pathogens, including those never before encountered, and concurrently avoiding formation of antibodies binding host tissues. The erse repertoire of antibodies produced by V(D)J recombination inevitably includes autoantibodies that bind to self-antigens, estimated to be as much as 70% of nascent antibodies on immature B cells. Early theoretical models of tolerance hypothesized that such self-reactive clones could not possibly be allowed to survive and mature. However from the first direct view of the fate of nascent B cells carrying a self-binding antibody it was clear that many "forbidden clones" circulate to secondary lymphoid tissues, where they adopt an IgM
Publisher: Cold Spring Harbor Laboratory
Date: 26-08-2017
DOI: 10.1101/181156
Abstract: The B-cell receptor (BCR) performs essential functions for the adaptive immune system including recognition of pathogen-derived antigens. Cell-to-cell variability of BCR sequences due to V(D)J recombination and somatic hypermutation (SHM) necessitates single-cell characterization of BCR sequences. Single-cell RNA sequencing (scRNA-seq) presents the opportunity for simultaneous capture of the BCR sequence and transcriptomic signature for a detailed understanding of the dynamics of an immune response. We developed VDJPuzzle 2.0, a bioinformatic tool that reconstructs productive, full-length B-cell receptor sequences of both heavy and light chains. VDJPuzzle successfully reconstructs BCRs from 98.3% (n=117) of human and 96.5% (n=200) from murine B cells. 92.0% of clonotypes and 90.3% of mutations were concordant with single-cell Sanger sequencing of the immunoglobulin chains. VDJPuzzle is available at irbyvisp/vdjpuzzle2
Publisher: Elsevier BV
Date: 12-2016
Publisher: The American Association of Immunologists
Date: 07-2011
Abstract: One mechanism to molecularly explain the strong association of maternal anti-Ro60 Abs with cardiac disease in neonatal lupus (NL) is that these Abs initiate injury by binding to apoptotic cardiomyocytes in the fetal heart. Previous studies have demonstrated that β2-glycoprotein I (β2GPI) interacts with Ro60 on the surface of apoptotic Jurkat cells and prevents binding of anti-Ro60 IgG. Accordingly, the current study was initiated to test two complementary hypotheses, as follows: 1) competition between β2GPI and maternal anti-Ro60 Abs for binding apoptotic induced surface-translocated Ro60 occurs on human fetal cardiomyocytes and 2) circulating levels of β2GPI influence injury in anti-Ro60–exposed fetuses. Initial flow cytometry experiments conducted on apoptotic human fetal cardiomyocytes demonstrated dose-dependent binding of β2GPI. In competitive inhibition experiments, β2GPI prevented opsonization of apoptotic cardiomyocytes by maternal anti-Ro60 IgG. ELISA was used to quantify β2GPI in umbilical cord blood from 97 neonates exposed to anti-Ro60 Abs, 53 with cardiac NL and 44 with no cardiac disease. β2GPI levels were significantly lower in neonates with cardiac NL. Plasmin-mediated cleavage of β2GPI prevented binding to Ro60 and promoted the formation of pathogenic anti-Ro60 IgG-apoptotic cardiomyocyte complexes. In aggregate these data suggest that intact β2GPI in the fetal circulation may be a novel cardioprotective factor in anti-Ro60–exposed pregnancies.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.FOODCHEM.2019.01.134
Abstract: Different formulations and crystallising conditions were employed to vary the bulk phase structuring of oleogels. The oleogels were formed only at monoacylglycerol:native phytosterol (MAG:NPS) ratios of 10:0, 7:3 and 5:5. NPS co-crystallised with MAG in the oleogel mixtures and influenced the growth of lipidic crystal network. Faster cooling rates caused smaller crystals whereas thermal history affected the rigidity of oleogel s les. The oleogel s les were whipped and characterised for whipping time, foam overrun, microstructure, rheology and half-life of foam. The whipped oleogels were structured by layer(s) of lipidic crystals surrounding the air bubbles, which had non-spherical shapes and rough textures. The whipping time was remarkably reduced by 80% in the oleogel s les containing smaller lipidic crystals. All whippable oleogel s les had similar foam overrun values and extremely stable against foam collapse. The obtained oil foams exhibited liquid-like behaviour at low frequency as measured by the frequency sweep test.
Publisher: Oxford University Press (OUP)
Date: 18-04-2013
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.MEATSCI.2019.02.024
Abstract: Post-processing feasibility studies the integrity of the designed internal and external structures of 3D printed products. This study examined the effect of infill density (50%, 75%, 100%) and fat content (0, 1, 2, 3 fat layers within a structure) on the post-processing physical changes and texture of lean meat-lard composite layer 3D printed meat products cooked sous-vide. Data from raw and cooked s les were collected to determine cooking loss, shrinkage, moisture retention, fat retention, hardness, chewiness, and cohesiveness. 3D printed objects were successfully cooked, maintaining the internal and external structures. Infill density contributed proportionally (P < .05) to moisture retention, hardness and chewiness, and inversely (P < .05) to shrinkage and cohesiveness, with no effect on fat retention. Whereas, the fat content influenced proportionally (P < .05) to cooking loss, shrinkage, and cohesiveness, and inversely (P < .05) to fat and moisture retention, hardness, and chewiness. The interaction of both independent variables showed a significant effect (P < .05) on all the responses, except for fat retention.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2015
Publisher: Wiley
Date: 04-06-2021
DOI: 10.1111/IMCB.12478
Abstract: The level of immunoglobulin M (IgM) displayed on the surface of peripheral blood B cells exhibits a broad dynamic range and has been associated with both development and selection. To determine whether IgM surface expression associates with distinct immunoglobulin heavy‐chain (IGH) repertoire properties, we performed deep IgM sequencing of peripheral blood transitional and mature naïve B cells in the upper and lower quartiles of surface IgM expression for 12 healthy donors. Mature naïve B cells within the lowest quartile for surface IgM expression displayed more erse IGH features including increased complementarity‐determining region 3 length, IGHJ6 segment usage and aromatic amino acids compared with mature naïve B cells with high surface IgM. There were no differences between IGH repertoires for transitional B cells with high or low surface IgM. These findings suggest that a selection checkpoint during progression of transitional to mature naïve B cells reduces the breadth of the IGH repertoire among high surface IgM B cells but that ersity is preserved in B cells expressing low levels of surface IgM.
Publisher: Society for Neuroscience
Date: 03-12-2008
DOI: 10.1523/JNEUROSCI.4489-08.2008
Abstract: Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly to isolated mouse colons undergoing CMMC activity to test for autoantibodies that disrupt colonic motility. The effect of immunoglobulins prepared for clinical intravenous treatment (IVIg) on autoantibody-mediated colonic disruption was also assessed. Narcoleptic IgGs markedly reduced the frequency of CMMCs or irreversibly abolished them. Abrogation of CMMCs was followed by an increase in the resting tension of the colon preparation and appearance of atropine-sensitive phasic smooth muscle contractions. IVIg partially neutralized the inhibitory effect of narcoleptic IgG on the CMMCs. The dramatic effect of narcoleptic IgG on CMMC generation is consistent with an autoantibody-mediated disruption of enteric neural pathways. The ex vivo whole-organ approach allows real-time examination of the physiological effects of the narcoleptic autoantibody and offers a new avenue for exploring the autoimmune basis of narcolepsy. The neutralizing effect of IVIg on the autoantibody provides a rationale for the reported clinical improvement in cataplexy when IVIg are given at disease onset.
Publisher: Wiley
Date: 17-01-2012
DOI: 10.1038/ICB.2011.108
Publisher: Wiley
Date: 27-08-2020
Publisher: Springer New York
Date: 2018
DOI: 10.1007/978-1-4939-8648-4_15
Abstract: Here we describe methods for screening human blood to isolate peripheral blood mononuclear cells (PBMCs) capable of binding fluorescently labeled antigen, as well as methods for the lification and sequencing of B cell receptor (BCR) heavy and light chain genes. Detailed protocols are provided for transient mammalian expression in a hexahistidine-tagged Fab format, purification by immobilized metal affinity chromatography (IMAC), and affinity determination by BioLayer interferometry (BLI).
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 27-03-2008
DOI: 10.1002/ART.23377
Publisher: The Journal of Rheumatology
Date: 15-10-2023
Publisher: Oxford University Press (OUP)
Date: 07-02-2007
DOI: 10.1111/J.1365-2249.2007.03331.X
Abstract: Opsonization of apoptotic cardiocytes by maternal anti-Ro/SSA and anti-La/SSB antibodies contributes to tissue injury in the neonatal lupus syndrome. The objective of the current study was to quantify the surface membrane expression of Ro/La components during different phases of apoptosis and map the Ro/La apotopes (epitopes expressed on apoptotic cells) bound by cognate antibodies. Multi-parameter flow cytometry was used to define early and late apoptotic populations and their respective binding by monospecific anti-Ro and anti-La IgGs. Anti-Ro60 bound specifically to early apoptotic Jurkat cells and remained accessible on the cell surface throughout early and late apoptosis. In contrast, anti-La bound exclusively to late apoptotic cells in experiments controlled for non-specific membrane leakage of IgG. Ro52 was not accessible for antibody binding on either apoptotic population. The immunodominant NH2-terminal and RNA recognition motif (RRM) epitopes of La were expressed as apotopes on late apoptotic cells, confirming recent in vivo findings. An immunodominant internal epitope of Ro60 that contains the RRM, and is recognized by a majority of sera from mothers of children with congenital heart block (CHB) and patients with primary Sjögren's syndrome, was also accessible as an apotope on early apoptotic cells. The distinct temporal expression of the immunodominant Ro60 and La apotopes indicates that these intracellular autoantigens translocate independently to the cell surface, and supports a model in which maternal antibody populations against both Ro60 and La apotopes act in an additive fashion to increase the risk of tissue damage in CHB.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 10-2020
Publisher: SAGE Publications
Date: 02-11-2010
Publisher: Springer Science and Business Media LLC
Date: 20-02-2020
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 05-2017
Publisher: Wiley
Date: 03-08-2018
DOI: 10.1002/ART.40539
Abstract: Rheumatoid factors (RFs) are associated with systemic disease in primary Sjögren's syndrome (SS) and may be pathogenic as mixed cryoglobulins. Current detection methods cannot resolve RFs at a molecular level. This study was undertaken to perform the first proteomic and transcriptomic analysis of secreted and membrane-bound IgM-RF in primary SS and identify unique heavy-chain peptide signatures for RF clonotype tracking. Purified heavy chains of serum RFs from 15 patients with primary SS were subjected to de novo mass spectrometric sequencing. The circulating B cell Ig repertoire was determined by massively parallel sequencing of IGH RNA from matched peripheral blood mononuclear cells (n = 7). RF-specific heavy-chain third complementarity-determining region (CDR3) peptides were identified by searching RF heavy-chain peptide sequences against the corresponding IGH RNA sequence libraries. Heavy-chain CDR3 peptides were used as biomarkers to track serum RF clonotypes using quantitative multiple reaction monitoring. Serum RFs were clonally restricted and composed of shared sets of IgM heavy-chain variable region (Ig V Cryoprecipitable RF clonotypes linked to vasculitis in primary SS have different molecular profiles than nonprecipitating RFs, suggesting different underlying mechanisms of production. The combined omics workflow presented herein provides molecular biomarkers for tracking and removal of pathogenic RF clones.
Publisher: Wiley
Date: 09-01-2022
DOI: 10.1111/IMR.13064
Abstract: Autoimmune diseases are characterized by serum autoantibodies, some of which are pathogenic, causing severe manifestations and organ injury. However, autoantibodies of the same antigenic reactivity are also present in the serum of asymptomatic people years before they develop any clinical signs of autoimmunity. Autoantibodies can arise during multiple stages of B cell development, and various genetic and environmental factors drive their production. However, what drives the development of pathogenic autoantibodies is poorly understood. Advances in single‐cell technology have enabled the deep analysis of rare B cell clones producing pathogenic autoantibodies responsible for vasculitis in patients with primary Sjögren's syndrome complicated by mixed cryoglobulinaemia. These findings demonstrated a cascade of genetic events involving stereotypic immunoglobulin V(D)J recombination and transforming somatic mutations in lymphoma genes and V(D)J regions that disrupted antibody quality control mechanisms and decreased autoantibody solubility. Most studies consider V(D)J mutations that enhance autoantibody affinity to drive pathology however, V(D)J mutations that increase autoantibody propensity to form insoluble complexes could be a major contributor to autoantibody pathogenicity. Defining the molecular characteristics of pathogenic autoantibodies and failed tolerance checkpoints driving their formation will improve prognostication, enabling early treatment to prevent escalating organ damage and B cell malignancy.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Wiley
Date: 07-06-2010
Publisher: The American Association of Immunologists
Date: 07-2013
Abstract: Cardiac neonatal lupus (NL) is presumed to arise from maternal autoantibody targeting an intracellular ribonucleoprotein, Ro60, which binds noncoding Y RNA and only becomes accessible to autoantibodies during apoptosis. Despite the importance of Ro60 trafficking in the development of cardiac NL, the mechanism underlying cell surface exposure is unknown. To evaluate the influence of Y RNA on the subcellular location of Ro60 during apoptosis and activation of macrophages, stable Ro60 knockout murine fibroblasts expressing wild-type or mutated FLAG-Ro60 were assessed. FLAG3-Ro60(K170A R174A) binds Y RNA, whereas FLAG3-Ro60(H187S) does not bind Y RNA fibroblasts expressing these constructs showed equivalent intracellular expression of Ro60. In contrast, apoptotic fibroblasts containing FLAG3-Ro60(K170A R174A) were bound by anti-Ro60, whereas FLAG3-Ro60(H187S) was not surface expressed. RNA interference of mY3 RNA in wild-type fibroblasts inhibited surface translocation of Ro60 during apoptosis, whereas depletion of mY1 RNA did not affect Ro60 exposure. Furthermore, Ro60 was not exposed following overexpression of mY1 in the mY3-depleted fibroblasts. In an in vitro model of anti-Ro60–mediated injury, Y RNA was shown to be an obligate factor for TLR-dependent activation of macrophages challenged with anti-Ro60–opsonized apoptotic fibroblasts. Murine Y3 RNA is a necessary factor to support the surface translocation of Ro60, which is pivotal to the formation of immune complexes on apoptotic cells and a TLR-dependent proinflammatory cascade. Accordingly, the Y3 RNA moiety of the Ro60 ribonucleoprotein imparts a critical role in the pathogenicity of maternal anti-Ro60 autoantibodies.
Publisher: SPIE
Date: 21-12-2008
DOI: 10.1117/12.759260
Publisher: Elsevier BV
Date: 11-2008
Publisher: Rockefeller University Press
Date: 13-06-2016
DOI: 10.1084/JEM.20151978
Abstract: Clonal anergy is an enigmatic self-tolerance mechanism because no apparent purpose is served by retaining functionally silenced B cells bearing autoantibodies. Human autoantibodies with IGHV4-34*01 heavy chains bind to poly-N-acetyllactosamine carbohydrates (I/i antigen) on erythrocytes and B lymphocytes, cause cold agglutinin disease, and are carried by 5% of naive B cells that are anergic. We analyzed the specificity of three IGHV4-34*01 IgG antibodies isolated from healthy donors immunized against foreign rhesus D alloantigen or vaccinia virus. Each IgG was expressed and analyzed either in a hypermutated immune state or after reverting each antibody to its unmutated preimmune ancestor. In each case, the preimmune ancestor IgG bound intensely to normal human B cells bearing I/i antigen. Self-reactivity was removed by a single somatic mutation that paradoxically decreased binding to the foreign immunogen, whereas other mutations conferred increased foreign binding. These data demonstrate the existence of a mechanism for mutation away from self-reactivity in humans. Because 2.5% of switched memory B cells use IGHV4-34*01 and & % of these have mutations that remove I/i binding, clonal redemption of anergic cells appears efficient during physiological human antibody responses.
Publisher: Proceedings of the National Academy of Sciences
Date: 08-07-2022
Abstract: Humans lack the capacity to produce the Galα1–3Galβ1–4GlcNAc (α-gal) glycan, and produce anti-α-gal antibodies upon exposure to the carbohydrate on a erse set of immunogens, including commensal gut bacteria, malaria parasites, cetuximab, and tick proteins. Here we use X-ray crystallographic analysis of antibodies from α-gal knockout mice and humans in complex with the glycan to reveal a common binding motif, centered on a germline-encoded tryptophan residue at Kabat position 33 (W33) of the complementarity-determining region of the variable heavy chain (CDRH1). Immunoglobulin sequencing of anti-α-gal B cells in healthy humans and tick-induced mammalian meat anaphylaxis patients revealed preferential use of heavy chain germline IGHV3-7, encoding W33, among an otherwise highly polyclonal antibody response. Antigen binding was critically dependent on the presence of the germline-encoded W33 residue for all of the analyzed antibodies moreover, introduction of the W33 motif into naive IGHV3-23 antibody phage libraries enabled the rapid selection of α-gal binders. Our results outline structural and genetic factors that shape the human anti-α-galactosyl antibody response, and provide a framework for future therapeutics development.
Publisher: Wiley
Date: 29-04-2010
DOI: 10.1002/ART.27370
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.MEATSCI.2019.03.005
Abstract: Three-dimensional printing (3DP) process stands as a developing technology for food manufacturing, which offers the opportunity to design novel food products with improved nutritional value and sensorial profile. This review analyses the potential applications of 3DP technology for meat processing and the elemental aspects affecting the printability and post-processing feasibility of 3D printed meat products. The combination of nutritionally balanced ingredients and novel internal structures may be schemed into a multi-material 3D model that meets special in idual needs, such as chewing and swallowing difficulties. Furthermore, a temperature-controlled extruder-type 3D printer built with multi-head system is suggested to suit the required conditions for meat safety and rheological requirements.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.CARBPOL.2019.05.031
Abstract: Cooked high-amylose rices have slower digestibility, giving nutritional benefits, but inferior eating qualities. Molecular structural mechanisms for this inferior eating quality are found here using structural analysis by size-exclusion chromatography of both the parent starch and starch leached during cooking. All commonly-accepted sensory attributes of cooked rice were characterized by a trained human panel. Hardness, with the strongest negative correlation with panelist preference, was the dominant but not sole factor determining palatability. Hardness was controlled by the amounts of medium and long amylopectin chains and amylose in the starch, and by amylose content and amount of longer amylopectin chains in the leachate. This gives knowledge and understanding of the molecular structural characteristics of starch controlling cooked-rice preference: not just high amylose but also other aspects of molecular structure. This can help rice breeders to target starch-synthesis genes to select slowly digested (healthier) rices with acceptable palatability.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.CELREP.2021.110259
Abstract: CD21
Publisher: Cold Spring Harbor Laboratory
Date: 31-01-2021
DOI: 10.1101/2021.01.29.428877
Abstract: PAX5 is the master transcription factor controlling B cell identity. In humans, mutations in PAX5 account for 30% of B cell acute lymphoblastic leukemia (B-ALL) cases. Investigating the causal effects of PAX5 mutations has however been difficult due to the premature lethality of Pax5 −/− mice. Here we describe a novel mouse strain with a premature STOP mutation in Pax5 (Y351*) that produces a truncated protein and reduction in protein function, yet still allows for some B cell development to occur. A population of uncommitted and multipotent CD19 + B220 − B cells develops in the bone marrow of homozygous mice leading to the development of B-ALL. We show that the tumors frequently acquire secondary mutations in Jak3 , and Ptpn11 highlighting key pathways interacting with PAX5 during malignant transformation. Analysis of the PAX5 Y351* mice provide insight not only into the functional consequence of reduced PAX5 activity on B cell development and identity, but also provides an avenue in which to study PAX5-driven B-ALL in mice. Reduction in PAX5 function in mice induces the development of uncommitted B cells that have multipotent and malignant potential.
Publisher: Elsevier BV
Date: 12-2009
Publisher: Wiley
Date: 26-02-2009
DOI: 10.1002/ART.24361
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.FOODRES.2018.12.049
Abstract: Although whey proteins have high biological value, their application to UHT processed high protein neutral beverages is limited due to their low heat stability. This research aimed to exploit the chaperone activity of caseins to improve UHT stability of whey proteins. UHT stability of reconstituted milk protein concentrate (RMPC), reconstituted whey protein concentrate (RWPC) and s les with various casein to whey protein ratios (C:W) (80:20 to 40:60) was studied. A 2% protein RWPC caused severe fouling suggesting its poor UHT stability. However, 10% protein RMPC was very stable (UHT run-time > 120 min). Inclusion of caseins caused stabilization of whey proteins to UHT processing and 10% protein C:W-50:50 was successfully processed for >120 min. Further increase in whey proteins proportion in milk protein dispersions caused a drop in run-times (below 120 min) and overall heat transfer co-efficient (OHTC), corresponding with increase in particle size and apparent viscosity. Presence of higher amounts of casein in the serum phase of s les caused formation of smaller protein aggregates (D(4,3) was 0.23 and 0.16 μm for supernatants of C:W-40:60 and RMPC, respectively) after heating. These results can help to increase the whey protein content of neutral pH, UHT processed high protein ready to drink beverages.
Publisher: Elsevier BV
Date: 03-2019
Publisher: Elsevier BV
Date: 09-2011
Publisher: Rockefeller University Press
Date: 16-12-2019
DOI: 10.1084/JEM.20191336
Abstract: Antibody-mediated autoimmune diseases are a major health burden. However, our understanding of how self-reactive B cells escape self-tolerance checkpoints to secrete pathogenic autoantibodies remains incomplete. Here, we demonstrate that patients with monogenic immune dysregulation caused by gain-of-function mutations in PIK3CD, encoding the p110δ catalytic subunit of phosphoinositide 3-kinase (PI3K), have highly penetrant secretion of autoreactive IgM antibodies. In mice with the corresponding heterozygous Pik3cd activating mutation, self-reactive B cells exhibit a cell-autonomous subversion of their response to self-antigen: instead of becoming tolerized and repressed from secreting autoantibody, Pik3cd gain-of-function B cells are activated by self-antigen to form plasmablasts that secrete high titers of germline-encoded IgM autoantibody and hypermutating germinal center B cells. However, within the germinal center, peripheral tolerance was still enforced, and there was selection against B cells with high affinity for self-antigen. These data show that the strength of PI3K signaling is a key regulator of pregerminal center B cell self-tolerance and thus represents a druggable pathway to treat antibody-mediated autoimmunity.
Publisher: Wiley
Date: 27-08-2012
DOI: 10.1002/ACR.21704
Publisher: Wiley
Date: 28-10-2011
DOI: 10.1002/ART.30566
Publisher: Springer Science and Business Media LLC
Date: 10-11-2016
DOI: 10.1038/NCOMMS13381
Abstract: Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1. IgD expressed on its own is nevertheless competent to induce calcium signalling and the core anergy mRNA response. Syndecan-1 induction correlates with reduction of surface IgM and is exaggerated without surface IgD in many transitional and mature B cells. These results show that IgD attenuates the response to self-antigen in anergic cells and promotes their accumulation. In this way, IgD minimizes tolerance-induced holes in the pre-immune antibody repertoire.
No related grants have been discovered for Joanne Reed.