GPR183
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GPR183
G-protein coupled receptor 183 also known as Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) is a protein (GPCR) expressed on the surface of some immune cells, namely B cells and T cells; in humans it is encoded by the ''GPR183'' gene. Expression of EBI2 is one critical mediator of immune cell localization within lymph nodes, responsible in part for the coordination of B cell, T cell, and dendritic cell movement and interaction following antigen exposure. EBI2 is a receptor for oxysterols. The most potent activator is 7α,25-dihydroxycholesterol (7α,25-OHC), with other oxysterols exhibiting varying affinities for the receptor. Oxysterol gradients drive chemotaxis, attracting the EBI2-expressing cells to locations of high ligand concentration. The GPR183 gene was identified due to its upregulation during Epstein-Barr virus infection of the Burkitt's lymphoma cell line BL41, hence its name: EBI2. Tissue distribution and function B cells EBI2 helps B cell ho ...
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BCL6
Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the ''BCL6'' gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to B cell proliferation. The ''deletion'' of BCL6 is known to lead to failure to germinal center formation in the follicles of the lymph nodes, preventing B cells from undergoing somatic hypermutation. ''Mutations'' in BCL6 can lead to B cell lymphomas because it promotes unchecked B cell growth. Clinically, BCL6 can be used to diagnose B cell lymphomas and is shown to be upregulated in a number of cancers. Other BCL genes, including BCL2, BCL3, BCL5, BCL7A, BCL9, and BCL10, also have clinical significance in lymphoma. Normal Physiological Function Structure The protein encoded by the BCL6 gene is a zinc finger transcription f ...
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G Protein-coupled Receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. Text was copied from this source, which is available under Attribution 2.5 Generic (CC BY 2.5) license. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and ...
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Germinal Center
Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, proliferate, differentiate, and mutate their antibody genes (through somatic hypermutation aimed at achieving higher affinity) during a normal immune response; most of the germinal center B cells (BGC) are removed by tingible body macrophages. The B cells develop dynamically after the activation of follicular B cells by T-dependent antigen. As they undergo rapid and mutative cellular division, B cells of the germinal center's dark zone are known as centroblasts. Once these B cells have stopped proliferating and moved to the light zone, they are known as centrocytes, and are subjected to selection by follicular helper T (TFH) cells in the presence of follicular dendritic cells (FDCs). Germinal centers are an important part of the B cell humoral ...
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Cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors, but generally not hormones or growth factors (despite some overlap in the terminology). Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell. They act through cell surface receptors and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and res ...
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HSD3B7
In enzymology, a cholest-5-ene-3β,7α-diol 3β-dehydrogenase () is an enzyme that catalyzes the chemical reaction :cholest-5-ene-3β,7α-diol + NAD+ \rightleftharpoons 7α-hydroxycholest-4-en-3-one + NADH + H+ Thus, the two substrates of this enzyme are cholest-5-ene-3β,7α-diol and NAD+, whereas its 3 products are 7α-hydroxycholest-4-en-3-one, NADH, and H+. The systematic name of this enzyme class is cholest-5-ene-3β,7α-diol:NAD+ 3-oxidoreductase. This enzyme is also called 3β-hydroxy-Δ5-C27-steroid oxidoreductase. The human version of this enzyme is known as hydroxy-Δ-5-steroid dehydrogenase, 3 β- and steroid delta-isomerase 7 or HSD3B7 which is encoded by the ''HSD3B7'' gene. Function This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. This enzyme is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogena ...
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Stromal Cell
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term ''stromal'' comes from Latin , "bed covering", and Ancient Greek , , "bed". Stromal cells are an important part of the body's immune response and modulate inflammation through multiple pathways. They also aid in differentiation of hematopoietic cells and forming necessary blood elements. The interaction between stromal cells and tumor cells is known to play a major role in cancer growth and progression. In addition, by regulating local cytokine networks (e.g. M-CSF, LIF), bone marrow stromal cells have been described to be ...
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CYP7B1
25-hydroxycholesterol 7-alpha-hydroxylase also known as oxysterol and steroid 7-alpha-hydroxylase is an enzyme that in humans is encoded by the ''CYP7B1'' gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Function This endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway of extrahepatic tissues, which converts cholesterol to bile acids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be involved in the development of atherosclerosis, neurosteroid metabolism and sex hormone synthesis. CYP7B was discovered by Stapleton in a screen for transcripts expressed differentially in rat hippocampus versus the remainder of the brain. The encoded polypeptide, initially designated hct-1 (hippocampus transcript 1), had ...
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Oxysterol
An oxysterol is a derivative of cholesterol obtained by oxidation involving enzymes and / or pro-oxidants. Such compounds play important roles in various biological processes such as cholesterol homeostasis, lipid metabolism (sphingolipids, fatty acids), apoptosis, autophagy, and prenylation of proteins; the mode of action of oxysterols in these effects is still poorly understood. Several oxysterols are associated with age-related diseases such as cardiovascular disease, eye disease (cataract, age-related macular degeneration), certain neurodegenerative diseases and cancers. The activities of oxysterols in these diseases could be due to their pro-oxidative and pro-inflammatory activities and their ability to act on cellular organelles (mitochondria, peroxisome, lysosome) that can contribute to activate apoptosis and autophagy. There are arguments supporting that oxysterols have important roles in atherosclerosis progression which is involved in several cardiovascular diseases. Ident ...
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Marginal Zone
The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen. (Some sources consider it to be the part of red pulp which borders on the white pulp, while other sources consider it to be neither red pulp nor white pulp.) A marginal zone also exists in lymph nodes. Structure It is composed of cells derived primarily from the myeloid compartment of bone marrow differentiation. More recently, a population of Neutrophil#Subpopulations, neutrophil-killers has been described to populate peripheral areas of the marginal zone. At least three distinct cellular markers can be used to identify cells of the marginal zone, MOMA-1, ERTR-9 and MARCO. Blood flow The marginal zone (MZ) is a highly transited area that receives large amounts of blood from the general circulation. Remarkably, the splenic Microvessel, microvasculature shows striking differences in mice and humans. In humans, the spleen receives blood from the splenic ar ...
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Affinity Maturation
In immunology, affinity maturation is the process by which TFH cell-activated B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response can elicit antibodies with several fold greater affinity than in a primary response. Affinity maturation primarily occurs on membrane immunoglobulin of germinal center B cells and as a direct result of somatic hypermutation (SHM) and selection by TFH cells. __TOC__ ''In vivo'' The process is thought to involve two interrelated processes, occurring in the germinal centers of the secondary lymphoid organs: # Somatic hypermutation: Mutations in the variable, antigen-binding coding sequences (known as complementarity-determining regions (CDR)) of the immunoglobulin genes. The mutation rate is up to 1,000,000 times higher than in cell lines outside the lymphoid system. ...
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CXCR5
C-X-C chemokine receptor type 5 (CXC-R5) also known as CD185 (cluster of differentiation 185) or Burkitt lymphoma receptor 1 (BLR1) is a G protein-coupled seven transmembrane receptor for chemokine CXCL13 (also known as BLC) and belongs to the CXC chemokine receptor family. It enables T cells to migrate to lymph node and the B cell zones. In humans, the CXC-R5 protein is encoded by the ''CXCR5'' gene. Tissue distribution and function The ''BLR1'' / ''CXCR5'' gene is specifically expressed in Burkitt's lymphoma and lymphatic tissues, such as follicles in lymph nodes as well as in spleen. The gene plays an essential role in B cell migration. Through CXCL13 secretions B cells are able to locate the lymph node. Additionally, some recent studies have suggested that CXCL13, through CXCR5, is capable of recruiting hematopoietic precursor cells (CD3− CD4+) which would cause the development of lymph nodes and Peyer's Patches. Other studies highlight the role of CXCR5 in T cells, ...
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Follicular B Helper T Cells
Follicular helper T cells (also known as follicular B helper T cells and abbreviated as TFH), are antigen-experienced CD4+ T cells found in the periphery within B cell follicles of secondary lymphoid organs such as lymph nodes, spleen and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5. Upon cellular interaction and cross-signaling with their cognate follicular (Fo B) B cells, TFH cells trigger the formation and maintenance of germinal centers through the expression of CD40 ligand (CD40L) and the secretion of IL-21 and IL-4. TFH cells also migrate from T cell zones into these seeded germinal centers, predominantly composed of rapidly dividing B cells mutating their Ig genes. Within germinal centers, TFH cells play a critical role in mediating the selection and survival of B cells that go on to differentiate either into long-lived plasma cells capable of producing high affinity antibodies against foreign antigen ...
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