Immunoglobulin class switching , also known as isotype switching , isotypic commutation or class-switch recombination ( CSR ), is a biological mechanism that changes a B cell 's production of immunoglobulin from one type to another, such as from the isotype IgM to the isotype IgG . During this process, the constant-region portion of the antibody heavy chain is changed, but the variable region of the heavy chain stays the same (the terms variable and constant refer to changes or lack thereof between antibodies that target different epitopes ). Since the variable region does not change, class switching does not affect antigen specificity. Instead, the antibody retains affinity for the same antigens, but can interact with different effector molecules.
23-457: (Redirected from IL3 ) IL-3 may refer to: Interleukin 3 Illinois's 3rd congressional district Illinois Route 3 See also [ edit ] Il Tre , or Il 3 [REDACTED] Topics referred to by the same term This disambiguation page lists articles associated with the same title formed as a letter–number combination. If an internal link led you here, you may wish to change
46-434: A mature B cell via its membrane-bound antibody molecule (or B cell receptor ) to generate the different classes of antibody, all with the same variable domains as the original antibody generated in the immature B cell during the process of V(D)J recombination , but possessing distinct constant domains in their heavy chains . Naïve mature B cells produce both IgM and IgD , which are the first two heavy chain segments in
69-495: A process known as isotype or class switching. During CSR, portions of the antibody heavy chain locus are removed from the chromosome , and the gene segments surrounding the deleted portion are rejoined to retain a functional antibody gene that produces antibody of a different isotype . Double-stranded breaks are generated in DNA at conserved nucleotide motifs, called switch (S) regions, which are upstream from gene segments that encode
92-411: A γ, α or ε constant region gene segment. The free ends of the DNA are rejoined by a process called non-homologous end joining (NHEJ) to link the variable domain exon to the desired downstream constant domain exon of the antibody heavy chain. In the absence of non-homologous end joining, free ends of DNA may be rejoined by an alternative pathway biased toward microhomology joins. With the exception of
115-511: Is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: after removal of the signal peptide sequence, the mature protein contains 133 amino acids in its polypeptide chain. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. The major function of IL-3 cytokine
138-407: Is capable of stimulating differentiation of immature myelomonocytic cells causing changes to the macrophage and granulocyte populations. IL-3 signaling is able to give rise to widest array of cell lineages which is why it has been independently named “multi-CSF” in some older literature. IL-3 also induces various effector functions in both immature and mature cells that more precisely modulate
161-463: Is ensured by high affinity between cell surface interleukin-3 receptor and IL-3. This high affinity receptor contains α and β subunits. IL-3 shares the β subunit with IL-5 and granulocyte-macrophage colony-stimulating factor ( GM-CSF ). This β subunit sharing explains the biological functional similarities of different hematopoietic growth factors. IL-3 receptors can be found on a variety of cell types including many immature myelomonocytic cells in
184-454: Is secreted by basophils and activated T cells to support growth and differentiation of T cells from the bone marrow in an immune response. Activated T cells can either induce their own proliferation and differentiation ( autocrine signaling), or that of other T cells ( paracrine signaling) – both involve IL-2 binding to the IL-2 receptor on T cells (upregulated upon cell activation, under
207-411: Is to regulate the concentrations of various blood-cell types. It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors . It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching . Interleukin 3 is an interleukin , a type of biological signal ( cytokine ) that can improve
230-481: The hemopoietic system such as hemopoietic progenitor cells, as well as certain myeloid progenitors, basophils , and eosinophils . IL-3/Receptor complex induces JAK2/STAT5 cell signalization pathway. It can stimulate transcription factor c‑myc (activation of gene expression) and Ras pathway (suppression of apoptosis). In the early 1960s Ginsberg and Sachs discovered that IL-3 is a potent mast cell growth factor produced from activated T cells . Interleukin 3
253-472: The S regions, converting the original C bases into deoxyuridine and allowing the uracil glycosylase to excise the base. This allows AP-endonucleases to cut the newly-formed abasic site, creating the initial SSBs that spontaneously form DSBs. The intervening DNA between the S-regions is subsequently deleted from the chromosome, removing unwanted μ or δ heavy chain constant region exons and allowing substitution of
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#1732881325737276-636: The body's natural response to disease as part of the immune system . In conjunction with other β common chain cytokines GM-CSF and IL-5 , IL-3 works to regulate the inflammatory response in order to clear pathogens by changing the abundance of various cell populations via binding at the interleukin-3 receptor . IL-3 is mainly produced by activated T cells with the goal of initiating proliferation of various other immune cell types. However, IL-3 has also been shown to be produced in IgG+ B cells and may be involved in earlier antibody isotype switching. IL-3
299-616: The body’s defense against microbial pathogens. IL-3 is also involved in the reconstruction of platelets via the development of megakaryocytes . Interleukin 3 stimulates the differentiation of multipotent hematopoietic stem cells into myeloid progenitor cells or, with the addition of IL-7, into lymphoid progenitor cells . In addition, IL-3 stimulates proliferation of all cells in the myeloid lineage ( granulocytes , monocytes , and dendritic cells ), in conjunction with other cytokines, e.g., Erythropoietin (EPO), Granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-6 . IL-3
322-479: The constant regions of antibody heavy chains ; these occur adjacent to all heavy chain constant region genes with the exception of the δ-chain. DNA is nicked and broken at two selected S-regions by the activity of a series of enzymes , including activation-induced (cytidine) deaminase (AID), uracil DNA glycosylase and apyrimidic/apurinic (AP)-endonucleases . AID begins the process of class switching by deaminating (removing an amino group from) cytosines within
345-416: The highly repetitive structure of the target S regions, the process of class switching needs S regions to be first transcribed and spliced out of the immunoglobulin heavy chain transcripts (where they lie within introns). Chromatin remodeling, accessibility to transcription and to AID and synapsis of broken S regions are under the control of a large super-enhancer, located downstream the more distal Calpha gene,
368-468: The immunoglobulin locus . After activation by antigen, these B cells proliferate. If these activated B cells encounter specific signaling molecules via their CD40 and cytokine receptors (both modulated by T helper cells ), they undergo antibody class switching to produce IgG, IgA or IgE antibodies. During class switching, the constant region of the immunoglobulin heavy chain changes but the variable regions do not, and therefore antigenic specificity, remains
391-505: The induction of macrophage -secreted IL-1 ). The human IL-3 gene encodes a protein 152 amino acids long, and the naturally occurring IL-3 is glycosylated. The human IL-3 gene is located on chromosome 5 , only 9 kilobases from the GM-CSF gene, and its function is quite similar to GM-CSF. IL-3 is a T cell-derived, pluripotent and hematopoietic factor required for survival and proliferation of hematopoietic progenitor cells. The signal transmission
414-528: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=IL-3&oldid=1108838613 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Interleukin 3 1JLI 3562 n/a ENSG00000164399 n/a P08700 n/a NM_000588 n/a NP_000579 n/a Interleukin 3 ( IL-3 )
437-480: The myelomonocytic leukaemia cell line WEHI-3B. It is thought that this genetic change is the key in development of this leukemia type. Human IL-3 was first cloned in 1986 and since then clinical trials are ongoing. Post-chemotherapy, IL-3 application reduces chemotherapy delays and promotes regeneration of granulocytes and platelets . However, only IL-3 treatment in bone marrow failure disorders such as myelodysplastic syndrome (MDS) and aplastic anemia (AA)
460-453: The same. This allows different daughter cells from the same activated B cell to produce antibodies of different isotypes or subtypes (e.g. IgG1, IgG2 etc.). In humans, the order of the heavy chain exons is as follows: Class switching occurs by a mechanism called class switch recombination (CSR) binding. Class switch recombination is a biological mechanism that allows the class of antibody produced by an activated B cell to change during
483-573: The μ and δ genes, only one antibody class is expressed by a B cell at any point in time. While class switch recombination is mostly a deletional process, rearranging a chromosome in "cis", it can also occur (in 10 to 20% of cases, depending upon the Ig class) as an inter-chromosomal translocation mixing immunoglobulin heavy chain genes from both alleles. T cell cytokines modulate class switching in mouse (Table 1) and human (Table 2). These cytokines may have suppressive effect on production of IgM. In addition to
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#1732881325737506-443: Was disappointing. It has been shown that combination of IL-3, GM-CSF and stem cell factor enhances peripheral blood stem cells during high-dose chemotherapy. Other studies showed that IL-3 could be a future perspective therapeutic agent in lymphohematopoietic disorders and solid cancers. Interleukin 3 has been shown to interact with IL3RA . Immunoglobulin class switching Class switching occurs after activation of
529-403: Was originally discovered in mice and later isolated from humans. The cytokine was originally discovered via the observation that it induced the synthesis of 20alpha-hydroxysteroid dehydrogenase in hematopoietic cells and termed it interleukin-3 (IL-3). IL-3 is produced by T cells only after stimulation with antigens or other specific impulses. However, it was observed that IL-3 is present in
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