Fiche publication
Date publication
novembre 2024
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MARTIN Thierry
Tous les auteurs :
Dieudonné Y, Lorenzetti R, Rottura J, Janowska I, Frenger Q, Jacquel L, Vollmer O, Carbone F, Chengsong Z, Luka M, Depauw S, Wadier N, Giorgiutti S, Nespola B, Herb A, Voll RE, Guffroy A, Poindron V, Ménager M, Martin T, Soulas-Sprauel P, Rizzi M, Korganow AS, Gies V
Lien Pubmed
Résumé
Primary antiphospholipid syndrome (PAPS) is a life-threatening clotting disorder mediated by pathogenic autoantibodies. Here we dissect the origin of self-reactive B cells in human PAPS using peripheral blood and bone marrow of patients with triple-positive PAPS via combined single-cell RNA sequencing, B cell receptors (BCR) repertoire profiling, CITEseq analysis and single cell immortalization. We find that antiphospholipid (aPL)-specific B cells are present in the naive compartment, polyreactive, and derived from the natural repertoire. Furthermore, B cells with aPL specificities are not eliminated in patients with PAPS, persist until the memory and long-lived plasma cell stages, likely after defective germinal center selection, while becoming less polyreactive. Lastly, compared with the non-PAPS cells, PAPS B cells exhibit distinct IFN and APRIL signature as well as dysregulated mTORC1 and MYC pathways. Our findings may thus elucidate the survival mechanisms of these autoreactive B cells and suggest potential therapeutic targets for the treatment of PAPS.
Mots clés
Humans, Germinal Center, immunology, Antiphospholipid Syndrome, immunology, B-Lymphocytes, immunology, Female, Adult, Middle Aged, Male, Antibodies, Antiphospholipid, immunology, Receptors, Antigen, B-Cell, metabolism, Single-Cell Analysis, Autoantibodies, immunology, Aged
Référence
Nat Commun. 2024 11 15;15(1):9921
