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- W3027300837 endingPage "642" @default.
- W3027300837 startingPage "629" @default.
- W3027300837 abstract "The generation of a diverse antibody repertoire is crucial for the adaptive immune system and is accomplished through sequential V(D)J recombination of loci encoding the immunoglobulin heavy (IgH) and light chain (Igκ and Igλ). The tight regulation and separation of proliferation and differentiation processes during B cell development is crucial for avoiding genomic instability. Previous models identified two receptors, IL-7R and the pre-BCR, as being essential in the regulation of the pre-B cell checkpoint. However, new research has brought to light the crucial role of a third receptor, CXCR4, in mouse models. CXCR4 drives the positioning of developing B cells within specific microniches in the murine BM. CXCR4 then mediates a feed-forward loop initiated by the pre-BCR that coordinates cell-cycle exit and pre-BCR repression. CXCR4 is also crucial for Igκ recombination and for inducing the pathways to recruit the required transcription factors and chromatin remodeling complexes. As the unique source of diverse immunoglobulin repertoires, B lymphocytes are an indispensable part of humoral immunity. B cell progenitors progress through sequential and mutually exclusive states of proliferation and recombination, coordinated by cytokines and chemokines. Mutations affecting the crucial pre-B cell checkpoint result in immunodeficiency, autoimmunity, and leukemia. This checkpoint was previously modeled by the signaling of two opposing receptors, IL-7R and the pre-BCR. We provide an update to this model in which three receptors, IL-7R, pre-BCR, and CXCR4, work in concert to coordinate both the proper positioning of B cell progenitors in the bone marrow (BM) microenvironment and their progression through the pre-B checkpoint. Furthermore, signaling initiated by all three receptors directly instructs cell fate and developmental progression. As the unique source of diverse immunoglobulin repertoires, B lymphocytes are an indispensable part of humoral immunity. B cell progenitors progress through sequential and mutually exclusive states of proliferation and recombination, coordinated by cytokines and chemokines. Mutations affecting the crucial pre-B cell checkpoint result in immunodeficiency, autoimmunity, and leukemia. This checkpoint was previously modeled by the signaling of two opposing receptors, IL-7R and the pre-BCR. We provide an update to this model in which three receptors, IL-7R, pre-BCR, and CXCR4, work in concert to coordinate both the proper positioning of B cell progenitors in the bone marrow (BM) microenvironment and their progression through the pre-B checkpoint. Furthermore, signaling initiated by all three receptors directly instructs cell fate and developmental progression. an enzyme that helps to maintain homeostasis of cellular energy by activating glucose and fatty acid uptake and oxidation. can give rise to B cells, T cells, dendritic cells, and natural killer cells, but lack myeloid and erythroid potential. a cytoplasmic tyrosine kinase that contributes to integrin-mediated signal transduction and migration by regulating actin cytoskeleton remodeling. a dynamic epigenetic modification of chromatin in which lysine residue(s) of histone molecules are reversibly acetylated by histone acetyltransferases; acetylation is generally associated with permissive activation of gene regulatory regions. a post-translational histone modification of a lysine residue on the amino-terminal tail of histone 3; H3Ac is considered to be a mark of transcriptionally active chromatin. the process of large-scale contraction of the immunoglobulin heavy-chain (IgH) locus in developing B cells that are poised to undergo IgH V(D)J recombination. This contraction brings the recombining V, D, and J loci into close 3D proximity. conserved sequences of four amino acids in the cytoplasmic tails of non-catalytic tyrosine-phosphorylated receptors. They are important for signal transduction in immune cells. a serine/threonine protein kinase and member of the PI3K-related kinase family that regulates cell growth, proliferation, motility, survival, transcription, and protein synthesis. antibody gene rearrangement in a B lymphocyte to replace an already existing antigen receptor to mitigate autoreactivity. a family of non-receptor tyrosine kinases that includes nine members: SRC, YES, FYN, FGR, LCK, HCK, BLK, and LYN. two highly related proteins. Once phosphorylated and activated, STAT5 proteins dimerize and bind to DNA response elements, inducing transcription of their target genes. transcription foci or discrete sites where transcription occurs in the nucleus; in transcription factories several RNA polymerases are thought to be associated with the nuclear matrix." @default.
- W3027300837 created "2020-05-29" @default.
- W3027300837 creator A5047081840 @default.
- W3027300837 creator A5064934512 @default.
- W3027300837 date "2020-07-01" @default.
- W3027300837 modified "2023-10-17" @default.
- W3027300837 title "It Takes Three Receptors to Raise a B Cell" @default.
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