Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression.
Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression.
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RA滑膜中异位淋巴B细胞活化和高突变的动态谱，以NR 4A核受体表达为特征
DOI：
10.1016/j.celrep.2022.110766
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发表时间：
2022-05-03
期刊：
影响因子：
8.8
通讯作者：
Anolik, Jennifer H.
中科院分区：
文献类型：
--
作者：
Meednu, Nida;Rangel-Moreno, Javier;Zhang, Fan;Escalera-Rivera, Katherine;Corsiero, Elisa;Prediletto, Edoardo;DiCarlo, Edward;Goodman, Susan;Donlin, Laura T.;Raychauduri, Soumya;Bombardieri, Michele;Pitzalis, Costantino;Orange, Dana E.;McDavid, Andrew;Anolik, Jennifer H.
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 α and β 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. Meednu et al. identify a B cell population in the RA synovium with upregulation of the NR4A gene family. The population displays a continuum of somatic hypermutation—pointing to in situ activation—with NR4A expression a readout of antigen stimulation and pathological B cell responses.
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