A5011675080- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Leprosy Research and Treatment
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Mycobacterium research and diagnosis
- Diabetes and associated disorders
- Tuberculosis Research and Epidemiology
- Allergic Rhinitis and Sensitization
- Macrophage Migration Inhibitory Factor
- Glycosylation and Glycoproteins Research
- Animal Genetics and Reproduction
- Transgenic Plants and Applications
- CAR-T cell therapy research
- Xenotransplantation and immune response
- Food Allergy and Anaphylaxis Research
- Chronic Lymphocytic Leukemia Research
- Systemic Lupus Erythematosus Research
- Blood groups and transfusion
- Asthma and respiratory diseases
- Yersinia bacterium, plague, ectoparasites research
- Cancer Immunotherapy and Biomarkers
- Platelet Disorders and Treatments
St Vincent's Clinic
2009-2022
Garvan Institute of Medical Research
2006-2022
UNSW Sydney
2009-2022
Centenary Institute
1997-2014
The University of Sydney
1989-2008
Royal Prince Alfred Hospital
1978-2001
Turku University Hospital
2001
University of California, San Francisco
1998
Walter and Eliza Hall Institute of Medical Research
1970-1995
The Royal Melbourne Hospital
1971-1995
In transgenic mice, self-reactive B lymphocytes are eliminated if they encounter membrane-bound self antigens during their development within the bone marrow. We show here that two separate and sequential events, arrested cell death, bring about elimination. Developmental arrest is an early outcome of antigen binding in immature cells, blocks acquisition adhesion molecules receptors important for migration activation, rapidly reversible by removal antigen. Death cells occurs 1 to 3 days can...
B cells responding to T-dependent antigen either differentiate rapidly into extrafollicular plasma or enter germinal centers and undergo somatic hypermutation affinity maturation. However, the physiological cues that direct cell differentiation down one pathway versus other are unknown. Here we show strength of initial interaction between receptor (BCR) is a primary determinant this decision. expressing defined BCR specificity for hen egg lysozyme (HEL) were challenged with sheep red blood...
Evidence is presented for the existence on all B lymphocytes, but not T of a membrane-associated receptor antibody. The was detected by radioautographic technique in which lymphoid cells were incubated with antibody followed corresponding radioiodinated antigen. ease eluted during washing indicated that bond between and cell weak. formation an antibody-antigen complex surface, however, stabilized permitted accurate quantitation adherent ability several combinations antigen to adhere...
Whether radiofrequency (RF) fields are carcinogenic is controversial; epidemiological data have been inconclusive and animal tests limited. The aim of the present study was to determine whether long-term exposure pulse-modulated RF similar those used in digital mobile telecommunications would increase incidence lymphoma E mu-Pim1 transgenic mice, which moderately predisposed develop spontaneously. One hundred female mice were sham-exposed 101 exposed for two 30-min periods per day up 18...
A possible role for the lymphocyte in mechanism of eosinopoiesis has been examined. Procedures known to deplete or inactivate pool recirculating lymphocytes such as neonatal thymectomy, administration antilymphocyte serum, and prolonged thoracic duct drainage, either singly combination, resulted a highly significant reduction eosinophil response trichinosis. Irradiated animals exposed parasitic challenge did not develop eosinophilia unless reconstituted with well bone marrow cells. When...
A hallmark of T cell–dependent immune responses is the progressive increase in ability serum antibodies to bind antigen and provide protection. Affinity maturation antibody response thought be connected with preferential survival germinal centre (GC) B cells that have acquired increased affinity for via somatic hypermutation their immunoglobulin genes. However, mechanisms drive remain obscure because difficulty tracking affinity-based selection GC differentiation into plasma cells. We...
Certain antigens such as polymerized flagellin are capable of producing relatively normal antibody levels in thymectomized mice, whereas others, including heterologous erythrocytes require the presence T cells a helper capacity. The mechanism thymus-independent production was investigated by comparing primary IgM responses spleen from ATXBM, XBM, and mice to various physical forms flagellar Salmonella adelaide vitro. No reduction antibody-forming cell over wide dose range observed ATXBM...
Plasma cells (PCs) derived from germinal centers (GCs) secrete the high-affinity antibodies required for long-term serological immunity. Nevertheless, process whereby GC B differentiate into PCs is uncharacterized, and mechanism underlying selective PC differentiation of only remains unknown. In this study, we show that induced among a discrete subset residing within light zone GC. Initiation signals delivered upon engagement with intact antigen. Signals by T follicular helper were not to...
The life span of anergic self-reactive B cells was determined by 5-bromo-2'-deoxyuridine (BrdU) loading tolerant double-transgenic (Dbl-Tg) mice produced mating hen egg lysozyme (HEL)-transgenic with the corresponding immunoglobulin-transgenic (Ig-Tg) mice, which express anti-HEL IgM and IgD. from Dbl-Tg despite being exposed to soluble antigen throughout their development, are not deleted, but persist in an state. As a prelude studying these cells, BrdU administered nontransgenic mice; bone...
Self-reactive B cells from tolerant double-transgenic (Dbl-Tg) mice coexpressing hen egg lysozyme (HEL) and rearranged anti-HEL immunoglobulin genes have a relatively short life span when compared to normal cells, irrespective of whether they are exposed antigen in multivalent membrane-bound form (mHEL-Dbl-Tg mice) or soluble (sHEL-Dbl-Tg mice). The factors responsible for determining the fate these after encounter with self-antigen were investigated using cell-tracking technique which Ig-Tg...
To optimize the initial wave of Ab production against T-dependent Ags, primary B cell clones with highest Ag affinity are selected to generate largest extrafollicular plasmablast (PB) responses. The mechanism behind this remains undefined, primarily due difficulty analyzing low frequency Ag-specific cells during earliest phases immune response when key differentiation decisions made. In study, a high resolution in vivo mouse model was used characterize detail first 6 days and identify steps...
In both humans and animals, immunoglobulin (Ig)G autoantibodies are less frequent but more pathogenic than IgM autoantibodies, suggesting that controls over Ig isotype switching required to reinforce B cell self-tolerance. We have used gene targeting produce mice in which hen egg lysozyme (HEL)-specific cells can switch all isotypes (SWHEL mice). When crossed with soluble HEL transgenic (Tg) mice, self-reactive SWHEL became anergic. However, contrast anergic from the original nonswitching...
The phenomenon of eosinophilia was studied in rats using inoculation with Trichinella larvae as the experimental stimulus. Comparisons were made between eosinophil response accompanying active infestation via gastrointestinal tract and that resulting from parenteral or their products. A vigorous could be provoked by a single intravenous injection intact parasites. In this circumstance lodged lungs causing an acute inflammatory reaction which led to disintegration within 24 hr. Intraaortic...
Self-tolerance to a transgene-encoded protein, hen egg lysozyme, was examined in the T and B cell repertoires of series lines transgenic mice that expressed different serum concentrations soluble lysozyme. cells were tolerant all which lysozyme irrespective antigen concentration, whereas tolerance did not occur when concentration less than 1.5 nanograms per milliliter (0.1 nM). Induction elevated transgene expression could restore tolerance. These findings support hypothesis autoimmune...