{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:06:01Z","timestamp":1783926361610,"version":"3.55.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Rheumatoid arthritis (RA) is characterized by persistent synovial inflammation in which fibroblast-like synoviocytes (RA-FLS) and B cells interact within a potentially genotoxic microenvironment. This study investigates how naive B cells respond to cytotoxic stress when supported by RA-FLS in a co-culture model, using viability assays, time resolved \u03b3-H2AX MFI, RT-qPCR of DNA damage response and differentiation genes, and flow cytometric analysis of subsets and surface markers. Naive B cells exhibited greater loss of viability than RA-FLS, and time-resolved \u03b3-H2AX MFI showed an earlier signal peak and decline in naive B cells versus prolonged retention in RA-FLS (0-24h post-treatment); these reflect overall damage-response dynamics rather than direct DSB repair. Importantly, \u03b3-H2AX levels indicate DNA damage but do not directly quantify DNA break repair. Transcriptional profiling showed selective induction of ATM, APEX1, RAD50, BAX, and BCL6 following treatment, consistent with engagement of a focused DNA damage response program. Prolonged co-culture was associated with the expansion of B cell enriched compartments derived from na\u00efve B cells, and with increased expression of stromal markers CD90 and podoplanin on both B cells and RA-FLS, while IL-10 secretion was reduced under cytotoxic conditions. Together, these findings define differential stress responses and phenotypic adaptations of B cells and RA-FLS within an inflammatory co-culture system and suggest that genotoxic stress may contribute to remodeling of immune-stromal interactions in the rheumatoid synovium.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1892572","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:17:40Z","timestamp":1783923460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotoxic stressors mimicking synovial microenvironment modulate B cell fate in RA-FLS co-culture"],"prefix":"10.3389","volume":"17","author":[{"given":"Denada","family":"Bruci","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Hiller Research Center, University Hospital D\u00fcsseldorf, Heinrich-Heine University D\u00fcsseldorf","place":["D\u00fcsseldorf, 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