A5065001474- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- Diabetes and associated disorders
- vaccines and immunoinformatics approaches
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood groups and transfusion
- RNA and protein synthesis mechanisms
- Cytomegalovirus and herpesvirus research
- Tryptophan and brain disorders
- CAR-T cell therapy research
- Respiratory viral infections research
- Protein purification and stability
- Chemokine receptors and signaling
- Complement system in diseases
- Chronic Lymphocytic Leukemia Research
- Systemic Lupus Erythematosus Research
- Artificial Immune Systems Applications
Duke University
2015-2025
Hsin Sheng College of Medical Care and Management
2021
International Vaccine Institute
2013-2019
Duke Medical Center
2008-2017
Duke University Hospital
2008-2017
Durham University
2013
Emory University
2011
Pediatrics and Genetics
2011
Durham VA Medical Center
2006
United States Department of Veterans Affairs
2001
After primary immunization with an immunogenic conjugate of (4-hydroxy-3-nitrophenyl)acetyl, two anatomically and phenotypically distinct populations antibody-forming cells arise in the spleen. As early as 2 d after immunization, foci antigen-binding B are observed along periphery periarteriolar lymphoid sheaths. These expand, occupying much 1% splenic volume by day 8 response. Later, grow smaller virtually absent from spleen 14. A second responding population, germinal center cells, appear...
B cell activation leads to proliferation and Ab production that can protect from pathogens or promote autoimmunity. Regulation of metabolism is essential support the demands lymphocyte growth effector function may regulate tolerance. In this study, we tested regulation role glucose uptake in control, anergic, autoimmune-prone cells. Control cells had a balanced increase lactate oxygen consumption following activation, with proportionally increased transporter Glut1 expression mitochondrial...
Costimulatory interactions between T and B lymphocytes are crucial for cell activation proliferation differentiation. We have compared the roles of CD40L B7-2 in initiation maturation humoral immunity by administering anti-CD40 ligand (L) or anti-B7-2 Ab during early (days -1 to 3) late 6-10) phases primary responses thymus-dependent (Td) -independent (Ti) Ags. Germinal center (GC) formation response a Td Ag was inhibited completely administration anti-CD40L Abs. Later response, established...
In the genetically restricted response that follows immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in spleens C57BL/6 mice. By 48 h postimmunization, foci antigen-binding appear along periphery periarteriolar lymphoid sheaths. These expand contain large numbers antibody-forming neither bind lectin, peanut agglutinin, nor mutate rearranged immunoglobulin variable region loci. Germinal centers containing...
V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known neutralizing has proven elusive, the induction with such specificity is important goal for vaccine development. A critical question which immunogens formulations might be used to trigger drive development memory B cell precursors specificity. In this paper we identified a clonal lineage four (CH01 CH04) from African HIV-1-infected broad...
In the murine spleen, germinal centers are anatomic sites for antigen-driven hypermutation and selection of immunoglobulin (Ig) genes. To detail kinetics Ig mutation selection, 178 VDJ sequences from 16 antigen-induced were analyzed. Although appeared by day 4, was not observed in center B cells until 8 postimmunization; thereafter, point mutations favoring asymmetrical transversions accumulated 14. During this period, strong phenotypic on mutant lymphocytes inferred progressively biased...
Abstract CD20 mAb-mediated B cell depletion is an effective treatment for malignancies and some autoimmune diseases. However, the full effects of on natural, primary, secondary Ab responses maintenance Ag-specific serum Ig levels are largely unknown. The relationship between memory cells, long-lived plasma humoral immunity also remains controversial. To address roles subsets in longevity responses, mature cells were depleted mice using mAb. Peritoneal reduced natural Ag-induced IgM...
The coordinated production of leukocytes in bone marrow is crucial for innate and adaptive immunity. Inflammation alters normal leukocyte by promoting granulopoiesis over lymphopoiesis, a response that supports the reactive neutrophilia follows infection. Here we demonstrate this specialization determined inflammation-induced reductions growth retention factors, most significantly stem cell factor CXCL12, which act preferentially to inhibit lymphoid development. These hierarchical effects...
Identification of maturation stages V3-glycan neutralizing antibodies explains the long duration required for their development.
Mice deficient in complement components C3 (C3 -/-) and C4 (C4 were found to have a profound defect their Ab response T-dependent Ag (bacteriophage (phi X174). Characterization of the mice demonstrated diminished level peanut agglutinin+ germinal centers failure isotype switching despite normal B cell signaling vitro. The nature was lie at level, as T cells primed C3- C4-deficient well those wild-type mice. These results, finding that could be partly reversed by 10-fold increase dose,...
To examine the role of germinal centers (GCs) in generation and selection high affinity antibody-forming cells (AFCs), we have analyzed average (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific AFCs serum antibodies both during after GC phase immune response. In addition, genetics NP-binding were followed to monitor at clonal level. gradually accumulate bone marrow (BM) immunization BM becomes predominant locale specific late primary Although NP-specific rapidly increased while GCs present (GC...
Reexpression of the V(D)J recombinase-activating genes RAG1 and RAG2 in germinal center B cells creates potential for immunoglobulin gene rearrangement generation new antigen receptor specificities. Intermediate products recombination are abundant a subset cells, demonstrating that κ light-chain locus becomes substrate renewed recombinase activity. This recombinationally active cell compartment contains many heavy-chain VDJ rearrangements encode low-affinity or nonfunctional antibody. In...
Affinity-driven selection of B lymphocytes within germinal centers is critical for the development high-affinity memory cells and host protection. To investigate role CD21/CD35 coreceptor in cell competition follicular retention survival center, either Cr2 + or null lysozyme-specific transgenic were adoptively transferred into normal mice immunized with duck (DEL) turkey (TEL) lysozyme, which bind different affinities. In injected responded by retention; however, they could not survive...
The products of the Rag1 and Rag2 genes drive genomic V(D)J rearrangements that assemble functional immunoglobulin T cell antigen receptor genes. Expression Rag has been thought to be limited developmentally immature lymphocyte populations in normal adult animals are primarily restricted bone marrow thymus. Abundant RAG1 RAG2 protein messenger RNA was detected activated B cells populate murine splenic Peyer's patch germinal centers. Germinal center thus share fundamental characteristics...