دورية أكاديمية
Single cell analysis of RA synovial B cells reveals a dynamic spectrum of ectopic lymphoid B cell activation and hypermutation characterized by NR4A nuclear receptor expression
| العنوان: | Single cell analysis of RA synovial B cells reveals a dynamic spectrum of ectopic lymphoid B cell activation and hypermutation characterized by NR4A nuclear receptor expression |
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| المؤلفون: | Meednu, N, Rangel-Moreno, J, Zhang, F, Escalera-Rivera, K, Corsiero, E, Prediletto, E, DiCarlo, E, Goodman, S, Donlin, L, Raychauduri, S, Bombardieri, M, Pitzalis, C, Orange, D, McDavid, A, Anolik, J, Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network |
| سنة النشر: | 2021 |
| المجموعة: | Queen Mary University of London: Queen Mary Research Online (QMRO) |
| مصطلحات موضوعية: | Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network |
| الوصف: | Ectopic lymphoid structures (ELS) can develop in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and selection are not well understood. Here, we identified a unique B cell population in the synovium characterized by co-expression of a family of orphan nuclear receptors, NR4A1 (also known as NUR77), NR4A2 (NURR1) and NR4A3 (NOR1), that is highly enriched at both early and late stages of RA. NR4A B cells are rare in healthy peripheral blood, RA blood, and SLE kidney, but share markers with blood transcriptomic signatures that peak during RA disease flare. Using combined single cell transcriptomics and B cell receptor (BCR) sequencing, we demonstrate that NR4A synovial B cells have an activated transcriptomic profile that significantly overlaps with germinal center (GC) light zone (LZ) B cells and an accrual of somatic hypermutation that correlates with loss of naïve B cell status. NR4A B cells uniquely co-express lymphotoxin β and IL6, supporting important functions in ELS promotion and pro-inflammatory cytokine production. Further, the presence of shared clones in this activated B cell state and NR4A expressing synovial plasma cells (PC) and the rapid up-regulation with BCR stimulation points to in situ differentiation. Taken together, we identified a dynamic progression of B cell activation in RA synovial ELS, with NR4A transcription factors having an important role in antigen activation and local adaptive immune responses. One sentence summary B cells in the rheumatoid arthritis synovium undergo a spectrum of in situ activation, with the NR4A family of transcription factors having an important role in antigen stimulation, local adaptive immunity, and pathological B cell responses. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://qmro.qmul.ac.uk/xmlui/handle/123456789/79768Test |
| DOI: | 10.1101/2021.05.14.443150 |
| الإتاحة: | https://doi.org/10.1101/2021.05.14.443150Test https://qmro.qmul.ac.uk/xmlui/handle/123456789/79768Test |
| رقم الانضمام: | edsbas.273D2304 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1101/2021.05.14.443150 |
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