A5080849379- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
- NF-κB Signaling Pathways
- Systemic Lupus Erythematosus Research
- Diabetes and associated disorders
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- Immune responses and vaccinations
- Cytomegalovirus and herpesvirus research
- Pediatric health and respiratory diseases
- Gut microbiota and health
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bacterial Genetics and Biotechnology
- Signaling Pathways in Disease
- Galectins and Cancer Biology
- Immune cells in cancer
- Microbial infections and disease research
- Hepatitis B Virus Studies
University of California, San Francisco
2012-2024
University of Pittsburgh
2023-2024
Universidad Católica de Santa Fe
2021
University of California System
2005-2017
University of Florida
2017
ThedaCare
2017
The University of Texas Southwestern Medical Center
2011
San Francisco Foundation
1996-2005
Cancer Research Institute
1995
Rockefeller University
1993
Receptors on macrophages for the Fc region of IgG (FcγR) mediate a number responses important host immunity. Signaling events necessary these are likely initiated by activation Src-family and Syk-family tyrosine kinases after FcγR cross-linking. Macrophages derived from Syk-deficient (Syk−) mice were defective in phagocytosis particles bound FcγRs, as well many FcγR-induced signaling events, including phosphorylation cellular substrates MAP kinases. In contrast, Syk− exhibited normal to...
Activation of macrophages by bacterial lipopolysaccharide (LPS) induces transcription genes that encode for proinflammatory regulators the immune response. Previous work has suggested activation factor activator protein 1 (AP-1) is one LPS-induced event mediates this Consistent with notion, we found LPS stimulated AP-1-mediated a transfected reporter gene in murine macrophage cell line RAW 264.7. As AP-1 activity regulated part c-Jun N-terminal kinase (JNK), which phosphorylates and...
LPS Activation of MAP Kinases in Macrophagesdifferent kinase isozymes.Thus, kinases are the first identified substrates for LPS-induced tyrosine phosphorylation.
The frequency of murine B lymphocytes that respond to antibodies directed against membrane IgM was measured. These anti-mu induced all, or almost resting cells enlarge over the first 24 h stimulation. This probably represents transition from state (G0) active transit through cell cycle. In contrast, only a fraction these cells, approximately 60% for BDF1 mice, continued cycle into S phase. is consistent with previous experiments had suggested there were some types did not proliferate in...
The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well potential pathogens. immune responses limit access these bacteria to underlying tissue remain poorly defined. Here we show γδ intraepithelial lymphocytes (γδ IEL) the small intestine produce innate antimicrobial factors in response resident "pathobionts" penetrate intestinal epithelium. IEL activation was dependent on epithelial cell-intrinsic MyD88, suggesting cells supply...
Macrophage Fcγ receptors (FcγRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, parasites. We examined FcγR signaling phagocytic function in bone marrow–derived macrophages from mutant mice lacking major Src family kinases expressed these cells, Hck, Fgr, Lyn. Many FcγR-induced functional responses events were diminished or delayed macrophages, including immunoglobulin (Ig)G-coated erythrocyte phagocytosis, respiratory burst, actin cup formation, activation Syk,...
Toll-like receptors (TLRs) are sensors for the detection of invading infectious agents and can initiate innate immune responses. Because system induces an appropriate defense against different pathogens, TLR signaling domains may have unique properties that responsible eliciting distinctive responses to types pathogens. To test this hypothesis, we created ligand-regulated chimeric composed extracellular region TLR4 transmembrane cytoplasmic regions other TLRs expressed these chimeras in...
Crosslinking membrane immunoglobulin (mIg), the B-cell antigen receptor, stimulates tyrosine phosphorylation of a number proteins. Since many receptors are phosphorylated after ligand binding, we asked if components mIg receptor complexes were tyrosine-phosphorylated crosslinking. Both mIgM and mIgD noncovalently associated with at least two other is MB-1 protein, which disulfide-linked to protein designated Ig-beta. not but IgD-alpha, also Using immunoprecipitation specific anti-MB-1...
Toll-like receptor (TLR) 3 and TLR7 are indispensable for host defense against viral infection by recognizing virus-derived RNAs localized to intracellular membranes via an unknown mechanism. We recently reported experiments with chimeric receptors that suggested the subcellular distribution of TLRs may be defined their transmembrane and/or cytoplasmic domains. Here we demonstrate localization TLR3 is achieved a 23-amino acid sequence (Glu(727) Asp(749)) present in linker region between...
In this report we have examined the ability of small resting B cells to act as antigen-presenting (APC) antigen-specific MHC-restricted T assessed by either cell proliferation or cell-dependent stimulation. We found that 10 14 in vitro clones and lines three four hybridomas could be induced proliferate secrete IL-2 presence lightly irradiated (1,000 rads) purified appropriate foreign antigen. All were stimulated make macrophage- dendritic cell-enriched populations all tested except one...
Abstract We have investigated the intracellular sources and physiological function of reactive oxygen species (ROS) produced in primary B cells response to BCR stimulation. stimulation resting murine induced rapid production ROS that occurred within minutes was maintained for at least 24 h after receptor While early (0–2 h) dependent on Nox2 isoform NADPH oxidase, later stages cell activation (6–24 were generated by a second pathway, which appeared be mitochondrial respiration. from mice...
The Lyn tyrosine kinase regulates inhibitory signaling in B and myeloid cells: loss of results a lupus-like autoimmune disease with hyperactive cells myeloproliferation. We have characterized the relative contribution Lyn-regulated pathways specifically to development autoimmunity by crossing novel lyn(flox/flox) animals mice carrying Cre recombinase under control Cd79a promoter, resulting deletion cells. specific is sufficient for immune complex-mediated glomerulonephritis. cell-specific...
Recent biochemical evidence indicates that an early event in signal transduction by the B-cell antigen receptor (BCR) is its translocation to specialized membrane subdomains known as lipid rafts. We have taken a microscopic approach image rafts and events associated with BCR transduction. Lipid were visualized on primary splenic B lymphocytes from wild-type or anti-hen egg lysozyme transgenic mice, mature mouse line Bal 17 using fluorescent conjugates of cholera toxin subunit Lyn-based...
Lipopolysaccharide, a component of the outer membrane Gram-negative bacteria, activates B lymphocytes and macrophages. Pertussis toxin, which inactivates several members G protein family signaling components, including Gi transducin, was found to inhibit lipopolysaccharide-induced responses WEHI-231 lymphoma cell line P388D1 macrophage line. These results, combined with demonstration that lipopolysaccharide inhibits adenylate cyclase activity in cells, strongly argues activation cells is...