期刊
CELL REPORTS
卷 39, 期 5, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2022.110766
关键词
-
类别
资金
- RUCCTS [UL1 TR001866, R01 AR078268-01A1]
- Robertson Foundation
- Bernard and Irene Schwartz Foundation
- University of Rochester CTSA award from the National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR002001]
- Bertha and Louis Weinstein research fund
- Accelerating Medicines Partnership (AMP) in RA and SLE Network
- National Institutes of Health [UH2-AR067676, UH2-AR067677, UH2-AR067679, UH2-AR067681, UH2-AR067685, UH2-AR067688, UH2-AR067689, UH2-AR067690, UH2-AR067691, UH2-AR067694, UM2-AR067678]
- [R21 AR071670]
A population of synovial B cells that co-express a family of orphan nuclear receptors has been identified, which plays an important role in local adaptive immune responses in rheumatoid arthritis (RA) synovial tissue.
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 identify a synovial B cell population characterized by co-expression of a family of orphan nuclear receptors (NR4A1-3), which is highly enriched in RA synovial tissue. A transcriptomic profile of NR4A synovial B cells significantly overlaps with germinal center light zone B cells and an accrual of somatic hypermutation that correlates with loss of naive B cell state. NR4A B cells co-express lymphotoxins a and b and IL-6, supporting functions in ELS promotion. Expanded and shared clones between synovial NR4A B cells and plasma cells and the rapid upregulation with BCR stimulation point to in situ differentiation. Together, we identify a dynamic progression of B cell activation in RA synovial ELS, with NR4A transcription factors having an important role in local adaptive immune responses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据