Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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.
Defective germinal center selection results in persistence of self-reactive B cells from the primary to the secondary repertoire in Primary Antiphospholipid Syndrome.
Nat Commun. 2024; 15(1): 9921
Doi: 10.1038/s41467-024-54228-8
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- Lorenzetti Raquel
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Germinal Center - immunology
- Antiphospholipid Syndrome - immunology
- B-Lymphocytes - immunology
- Female - administration & dosage
- Adult - administration & dosage
- Middle Aged - administration & dosage
- Male - administration & dosage
- Antibodies, Antiphospholipid - immunology
- Receptors, Antigen, B-Cell - metabolism, immunology
- Single-Cell Analysis - administration & dosage
- Autoantibodies - immunology
- Aged - administration & dosage