| http://purl.uniprot.org/citations/27501247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27501247 | http://www.w3.org/2000/01/rdf-schema#comment | "Germinal centres (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen-activated B cells proliferate, express high-affinity antibodies, promote antibody class switching, and yield B cell memory. Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class, both cell-autonomous and extrinsic metabolic programming have emerged as modulators of T-cell-mediated immunity. Here we show in mice that GC light zones are hypoxic, and that low oxygen tension () alters B cell physiology and function. In addition to reduced proliferation and increased B cell death, low impairs antibody class switching to the pro-inflammatory IgG2c antibody isotype by limiting the expression of activation-induced cytosine deaminase (AID). Hypoxia induces HIF transcription factors by restricting the activity of prolyl hydroxyl dioxygenase enzymes, which hydroxylate HIF-1α and HIF-2α to destabilize HIF by binding the von Hippel-Landau tumour suppressor protein (pVHL). B-cell-specific depletion of pVHL leads to constitutive HIF stabilization, decreases antigen-specific GC B cells and undermines the generation of high-affinity IgG, switching to IgG2c, early memory B cells, and recall antibody responses. HIF induction can reprogram metabolic and growth factor gene expression. Sustained hypoxia or HIF induction by pVHL deficiency inhibits mTOR complex 1 (mTORC1) activity in B lymphoblasts, and mTORC1-haploinsufficient B cells have reduced clonal expansion, AID expression, and capacities to yield IgG2c and high-affinity antibodies. Thus, the normal physiology of GCs involves regional variegation of hypoxia, and HIF-dependent oxygen sensing regulates vital functions of B cells. We propose that the restriction of oxygen in lymphoid organs, which can be altered in pathophysiological states, modulates humoral immunity."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature19334"xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Beck T.C."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Cho S.H."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Wei M."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Thomas J.W."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Boothby M.R."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Haase V.H."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Hiebert S."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Stengel K."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Volanakis E."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/author | "Raybuck A.L."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/name | "Nature"xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/pages | "234-238"xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/title | "Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system."xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://purl.uniprot.org/core/volume | "537"xsd:string |
| http://purl.uniprot.org/citations/27501247 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27501247 |
| http://purl.uniprot.org/citations/27501247 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27501247 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J1E9-mappedCitation-27501247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27501247 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J1F0-mappedCitation-27501247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27501247 |
| http://purl.uniprot.org/uniprot/#_A0A0N4SW09-mappedCitation-27501247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27501247 |
| http://purl.uniprot.org/uniprot/#_E0CYR1-mappedCitation-27501247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27501247 |
| http://purl.uniprot.org/uniprot/#_A0A991EQV1-mappedCitation-27501247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27501247 |