Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression.
Cell Rep
; 39(5): 110766, 2022 05 03.
Article
em En
| MEDLINE
| ID: mdl-35508128
ABSTRACT
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 ß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Membrana Sinovial
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos