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Although B cells expressing the IFNgR or the IFNg-inducible transcription factor T-bet drive autoimmunity in Systemic Lupus Erythematosus (SLE)-prone mouse models, the role for IFNg signaling in human antibody responses is unknown. We show that elevated levels of IFNg in SLE patients correlate with expansion of the T-bet expressing IgDCD27CD11cCXCR5 (DN2) pre-antibody secreting cell (pre-ASC) subset. We demonstrate that naïve B cells form T-bet pre-ASCs following stimulation with either Th1 cells or with IFNg, IL-2, anti-Ig and TLR7/8 ligand and that IL-21 dependent ASC formation is significantly enhanced by IFNg or IFNg-producing T cells. IFNg promotes ASC development by synergizing with IL-2 and TLR7/8 ligands to induce genome-wide epigenetic reprogramming of B cells, which results in increased chromatin accessibility surrounding IRF4 and BLIMP1 binding motifs and epigenetic remodeling of and loci. Finally, we show that IFNg signals poise B cells to differentiate by increasing their responsiveness to IL-21.
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Plasma cells (PCs) secrete large amounts of antibodies and develop from B cells that have been activated. PCs are rare cells located in the bone marrow or mucosa and ensure humoral immunity. Due to th...
Acute myeloid leukemia (AML) is a devastating hematological malignancy, characterized by differentiation arrest and unscheduled proliferation of immature cells of the myeloid lineage. Inducing AML cel...
The extracellular matrix plays a key role in stem cell maintenance, expansion, and differentiation. Laminin, a basement membrane protein, is a widely used substrate for cell culture including the grow...
Epigenetic regulation has been attracting increasing attention due to its role in cell differentiation and behaviors. However, the epigenetic mechanisms that regulate human dendritic cell (DC) differe...
Alcohol exposure induces TGFβ1 and renders the lung susceptible to injury and disrepair. We determined that TGFβ1 regulates myofibroblast differentiation through the loss of Thy-1 expression and con...
Female urinary incontinence and pelvic organ prolapse are common diseases especially in aged women that frequently cause urogenital infection, voiding difficulty, urinary retention, pelvic...
Determine the in-vivo mechanism of action of INF-B-1b as it's mechanisms of action are not completely understood. We propose that high dose exogenous recombinant IFN-B-1b induces tolerizin...
Human Tc17 cells (IL-17-producing CD8+ T cells) have been found to contribute to different kinds of human inflammatory and malignant diseases. Previous studies indicate that Tc17 cells can...
The investigators´ main hypothesis is that prenatal stress (PS)- induced programming during fetal and postnatal development is reflected in epigenetic and autonomic nervous system (ANS) b...
Stem cells can develop into every cell, every tissue and every organ in the human body, e.g., they can make any kind of cells in the human body. Stem cells reproduce themselves many times...
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.
A set of models of how communication impacts and is impacted by subjective experience. Techniques are generated from these models by sequencing of various aspects of the models in order to change someone's internal representations. Neurolinguistic programming is concerned with the patterns or programming created by the interactions among the brain, language, and the body, that produce both effective and ineffective behavior.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
A technique of operations research for solving certain kinds of problems involving many variables where a best value or set of best values is to be found. It is most likely to be feasible when the quantity to be optimized, sometimes called the objective function, can be stated as a mathematical expression in terms of the various activities within the system, and when this expression is simply proportional to the measure of the activities, i.e., is linear, and when all the restrictions are also linear. It is different from computer programming, although problems using linear programming techniques may be programmed on a computer.
A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...