{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:58:18Z","timestamp":1787068698586,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>In pro-B cells, VDJ recombination at the immunoglobulin heavy chain locus is impaired. B cell progenitor recombination implies the formation of DNA double strand breaks (DSBs) by the RAG recombinase, which are subsequently repaired by specific mechanisms. We cultured primary murine pro-B cells with IL-7 to evaluate H2AX histone phosphorylation, a well-established marker of DSB formation (\u03b3-H2AX foci) and the expression of proteins involved in DNA repair. Our results indicated that IL-7 upregulated the expression of several molecules involved in homologous recombination, the most accurate DSB repair mechanism. Quantitative analyses of \u03b3-H2AX foci revealed that IL-7 significantly increased DSB formation in a time-dependent manner. Furthermore, \u03b3-H2AX expression was altered in RAG2-deficient pro-B cells and absent in RAG1-deficient pro-B cells treated with IL-7, demonstrating the requirement of both RAG1 and RAG2 recombinase subunits. CD43 expression inversely correlates with the degree of cell differentiation and its level is often evaluated to assess the B lymphoid developmental stage. We observed that IL-7 upregulated CD43 expression and the percentage of large CD43\/\u03b3-H2AX double-positive cells, suggesting an effect on less differentiated, immature cells. Notably, we also found that IL-7 increased radiation-induced DSBs, while simultaneously supporting cell survival. This study uncovers novel effects of IL-7 on B cell differentiation, DSB formation, and DNA repair. It is well established that IL-7 promotes the proliferation and survival of acute lymphoblastic leukemia (ALL) cells. Our data suggest that drugs targeting IL-7 could improve ALL therapeutic protocols.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1633892","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T05:22:00Z","timestamp":1759728120000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["IL-7 promotes the formation of DNA double strand breaks and DNA repair in murine pro-B cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Alessia","family":"Lamolinara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Di Lisio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie 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