2024-03-28T18:16:17Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1693712020-12-13T09:15:35Zcom_10261_112com_10261_1com_10261_79col_10261_365col_10261_332
DIGITAL.CSIC
author
Mendoza, Pilar
author
Martínez-Martín, Nuria
author
Bovolenta, Paola
author
Reyes-Garau, Diana
author
Hernansanz-Agustín, Pablo
author
Delgado, Pilar
author
Díaz-Muñoz, Manuel D.
author
Oeste, Clara L.
author
Fernández-Pisonero, Isabel
author
Castellano, Esther
author
Martínez-Ruiz, Antonio
author
Alonso-López, D.
author
Santos de Dios, Eugenio
author
Bustelo, Xosé R.
author
Kurosaki, Tomohiro
author
Alarcón, Balbino
funder
European Research Council
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
funder
Red Temática de Investigación Cooperativa en Cáncer (España)
funder
Junta de Castilla y León
funder
Worldwide Cancer Research
funder
Fundación Ramón Areces
funder
Fundación Científica Asociación Española Contra el Cáncer
2018-09-04T09:26:17Z
2018-09-04T09:26:17Z
2018
Science Signaling 11(532): eaal1506 (2018)
http://hdl.handle.net/10261/169371
10.1126/scisignal.aal1506
http://dx.doi.org/10.13039/100008054http://dx.doi.org/10.13039/501100007287http://dx.doi.org/10.13039/501100004587http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/501100000781http://dx.doi.org/10.13039/501100002704http://dx.doi.org/10.13039/501100014180
29844052
Upon antigen recognition within peripheral lymphoid organs, B cells interact with T cells and other immune cells to transiently form morphological structures called germinal centers (GCs), which are required for B cell clonal expansion, immunoglobulin class switching, and affinity maturation. This process, known as the GC response, is an energetically demanding process that requires the metabolic reprogramming of B cells. We showed that the Ras-related guanosine triphosphate hydrolase (GTPase) R-Ras2 (also known as TC21) plays an essential, nonredundant, and B cell–intrinsic role in the GC response. Both the conversion of B cells into GC B cells and their expansion were impaired in mice lacking R-Ras2, but not in those lacking a highly related R-Ras subfamily member or both the classic H-Ras and N-Ras GTPases. In the absence of R-Ras2, activated B cells did not exhibit increased oxidative phosphorylation or aerobic glycolysis. We showed that R-Ras2 was an effector of both the B cell receptor (BCR) and CD40 and that, in its absence, B cells exhibited impaired activation of the PI3K-Akt-mTORC1 pathway, reduced mitochondrial DNA replication, and decreased expression of genes involved in glucose metabolism. Because most human B cell lymphomas originate from GC B cells or B cells that have undergone the GC response, our data suggest that R-Ras2 may also regulate metabolism in B cell malignancies.
eng
closedAccess
R-Ras2 is required for germinal center formation to aid B cells during energetically demanding processes
artículo
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URL
https://digital.csic.es/bitstream/10261/169371/1/accesoRestringido.pdf
File
MD5
42637ae8545636bc41605c1740a9a84e
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application/pdf
accesoRestringido.pdf