Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression

• DOI: 10.1016/j.celrep.2022.110766
• Publication Date: 2022-05-06T04:18:59Z
• Authors: Nida Meednu; Javier Rangel-Moreno; Fan Zhang; Katherine Escaler...; Elisa Corsiero; Edoardo Prediletto; Edward DiCarlo; Susan Goodman; Laura T. Donlin; Soumya Raychauduri; Michele Bombardieri; Costantino Pitzalis; Dana E. Orange; Andrew McDavid; Jennifer H. Anolik
• Keywords: Ectopic expression

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 population characterized by co-expression family orphan nuclear receptors (NR4A1-3), which is highly enriched RA tissue. A transcriptomic profile NR4A cells significantly overlaps with germinal center light zone an accrual somatic hypermutation that correlates loss naive state. co-express lymphotoxins α β IL-6, supporting functions ELS promotion. Expanded shared clones between plasma rapid upregulation BCR stimulation point to situ differentiation. Together, dynamic progression ELS, transcription factors having important role local adaptive immune responses.