2026-05-17T06:01:55Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/262252025-12-18T12:56:05Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Ortega-Molina, Ana author Lebrero-Fernández, Cristina author Sanz, Alba author Deleyto-Seldas, Nerea author Plata-Gómez, Ana Belén author Menéndez, Camino author Graña-Castro, Osvaldo author Caleiras, Eduardo author Efeyan, Alejo author 2021-07-13 B lymphocytes are exquisitely sensitive to fluctuations in nutrient signaling by the Rag GTPases, and 15% of follicular lymphomas (FLs) harbor activating mutations in RRAGC. Hence, a potential therapeutic approach against malignant B cells is to inhibit Rag GTPase signaling, but because such inhibitors are still to be developed, efficacy and safety remain unknown. We generated knockin mice expressing a hypomorphic variant of RagC (Q119L); RagC mice are viable and show attenuated nutrient signaling. B lymphocyte activation is cell-intrinsically impaired in RagC mice, which also show significant suppression of genetically induced lymphomagenesis and autoimmunity. Surprisingly, no overt systemic trade-offs or phenotypic alterations caused by partial suppression of nutrient signaling are seen in other organs, and RagC mice show normal longevity and normal age-dependent health decline. These results support the efficacy and safety of moderate inhibition of nutrient signaling against pathological B cells. Cell Rep . 2021 Jul 13;36(2):109372 Cell Rep 34260908 https://hdl.handle.net/20.500.12105/26225 B cell lymphoma RRAGC Rag GTPase aging cell growth germinal center longevity lymphocytes mTOR nutrient signaling Inhibition of Rag GTPase signaling in mice suppresses B cell responses and lymphomagenesis with minimal detrimental trade-offs.