143 research outputs found
Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy
No full textAdenosine deaminase (ADA) gene defects are among the most common causes of SCID. Restoration of purine metabolism and immune functions can be achieved by enzyme replacement therapy, or more effectively by bone marrow transplant or HSC gene therapy (HSC-GT). However, autoimmune complications and autoantibody production, including anti-nuclear antibodies (ANAs), frequently occur in ADA-SCID patients after treatment. To assess whether ADA deficiency affects the establishment of B cell tolerance, we tested the reactivity of recombinant antibodies isolated from single B cells of ADA-SCID patients before and after HSC-GT. We found that before HSC-GT, new emigrant/transitional and mature naive B cells from ADA-SCID patients contained more autoreactive and ANA-expressing clones, indicative of defective central and peripheral B cell tolerance checkpoints. We further observed impaired B cell receptor (BCR) and TLR functions in B cells after ADA inhibition, which may underlie the defects in B cell tolerance. Strikingly, after HSC-GT, ADA-SCID patients displayed quasi-normal early B cell tolerance checkpoints, as evidenced by restored removal of developing autoreactive and ANA-expressing B cells. Hence, ADA plays an essential role in controlling autoreactive B cell counterselection by regulating BCR and TLR functions
Reimagining What Images Can Achieve
No full textThe author discusses the ethics of the dissemination of ruin porn, focusing on the works of Philip Levine and Andrew Moore that document the crumbling and decaying ruins of buildings. She says that pornography it is not generally considered as acceptable despite its popularity. She adds that ruin porn is about the circulation of images of ruin buildings, such as the images of the decomposing Michigan Central Station and Packard Motor Plant by Yves Marchand and Roman Meffre
CVID-associated TACI mutations affect autoreactive B cell selection and activation
No full textCommon variable immune deficiency (CVID) is an assorted group of primary diseases that clinically manifest with antibody deficiency, infection susceptibility, and autoimmunity. Heterozygous mutations in the gene encoding the tumor necrosis factor receptor superfamily member TACI are associated with CVID and autoimmune manifestations, whereas two mutated alleles prevent autoimmunity. To assess how the number of TACI mutations affects B cell activation and tolerance checkpoints, we analyzed healthy individuals and CVID patients carrying one or two TACI mutations. We found that TACI interacts with the cleaved, mature forms of TLR7 and TLR9 and plays an important role during B cell activation and the central removal of autoreactive B cells in healthy donors and CVID patients. However, only subjects with a single TACI mutation displayed a breached immune tolerance and secreted antinuclear antibodies (ANAs). These antibodies were associated with the presence of circulating B cell lymphoma 6-expressing T follicular helper (Tfh) cells, likely stimulating autoreactive B cells. Thus, TACI mutations may favor CVID by altering B cell activation with coincident impairment of central B cell tolerance, whereas residual B cell responsiveness in patients with one, but not two, TACI mutations enables autoimmune complications
Impaired B‐cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies
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LES OUCHEBTIS MEMPHITES D’ÉPOQUE LIBYENNE : CARACTÉRISTIQUES TYPOLOGIQUES LOCALES
No full textInternational audienceLes caractéristiques stylistiques spécifiques des ouchebtis produits à Memphis à l’époque libyenne ont été isolées sur les exemplaires appartenant aux grands prêtres de Ptah ou découverts en fouilles. Ainsi mises en évidence, elles ont pu être repérées sur un ensemble de statuettes de prove- nance inconnue que leurs textes permettent d’identifier comme memphites. Ensuite, leur présence sur un groupe de statuettes de provenance inconnue dont les textes ne donnent aucune indication d’origine géographique permet de proposer de les rattacher à la production memphite. Enfin, ces caractéristiques sont comparées avec celles que l’on rencontre dans les autres centres de production d’époque libyenne.This study highlights the stylistic features of the Libyan Period shabtis made in Memphis recognizable on the statuettes made for the high priests of Ptah or found during excavations. In a second time, these features are picked out on statuettes of unknown provenance but bearing texts which point to a Memphite origin. Then, these features are recognized on a group of shabtis of unknown provenance bearing texts containing no geographic indication; their distinctive presence enabled the author to propose for them a Memphite origin. At the end, the Memphite features are compared with specific features of other production centres known during the Libyan Period
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