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Roco, Jonathan A.; Mesin, Luka; Binder, Sebastian C.; Nefzger, Christian; Gonzalez-Figueroa, Paula; Canete, Pablo F.; Ellyard, Julia; Shen, Qian; Robert, Philippe A.; Cappello, Jean; Vohra, Harpreet; Zhang, Yang; Nowosad, Carla R.; Schiepers, Arien; Corcoran, Lynn M.; Toellner, Kai-Michael; Polo, Jose M.; Meyer-Hermann, Michael; Victora, Gabriel D.; Vinuesa, Carola G.
Immunity (Cambridge, Mass.), 08/2019, Letnik: 51, Številka: 2Journal Article
Class-switch recombination (CSR) is a DNA recombination process that replaces the immunoglobulin (Ig) constant region for the isotype that can best protect against the pathogen. Dysregulation of CSR can cause self-reactive BCRs and B cell lymphomas; understanding the timing and location of CSR is therefore important. Although CSR commences upon T cell priming, it is generally considered a hallmark of germinal centers (GCs). Here, we have used multiple approaches to show that CSR is triggered prior to differentiation into GC B cells or plasmablasts and is greatly diminished in GCs. Despite finding a small percentage of GC B cells expressing germline transcripts, phylogenetic trees of GC BCRs from secondary lymphoid organs revealed that the vast majority of CSR events occurred prior to the onset of somatic hypermutation. As such, we have demonstrated the existence of IgM-dominated GCs, which are unlikely to occur under the assumption of ongoing switching. Display omitted •Germline transcripts peak prior to GC formation and rapidly decline in GCs•IgM-dominated clones are found in late GCs, arguing against ongoing Ig switching•CSR largely ceases upon the onset of somatic hypermutation•CSR decline due to low GLT and APE1 expression is possibly orchestrated by BCL6 Germinal centers (GCs) have long been considered sites in which Ig class-switch recombination (CSR) is favored. Roco et al. show that CSR occurs during the initial T cell:B cell interaction prior to GC formation and rapidly declines as B cells differentiate into GC cells and somatic hypermutation commences.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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