2024-03-28T16:29:40Zhttp://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
2018-09-04T09:26:17Z
urn:hdl:10261/169371
R-Ras2 is required for germinal center formation to aid B cells during energetically demanding processes
Mendoza, Pilar
Martínez-Martín, Nuria
Bovolenta, Paola
Reyes-Garau, Diana
Hernansanz-Agustín, Pablo
Delgado, Pilar
Díaz-Muñoz, Manuel D.
Oeste, Clara L.
Fernández-Pisonero, Isabel
Castellano, Esther
Martínez-Ruiz, Antonio
Alonso-López, D.
Santos de Dios, Eugenio
Bustelo, Xosé R.
Kurosaki, Tomohiro
Alarcón, Balbino
European Research Council
Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
Red Temática de Investigación Cooperativa en Cáncer (España)
Junta de Castilla y León
Worldwide Cancer Research
Fundación Ramón Areces
Fundación Científica Asociación Española Contra el Cáncer
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.
2018-09-04T09:26:17Z
2018-09-04T09:26:17Z
2018
2018-09-04T09:26:17Z
artículo
Science Signaling 11(532): eaal1506 (2018)
http://hdl.handle.net/10261/169371
10.1126/scisignal.aal1506
http://dx.doi.org/10.13039/100008054
http://dx.doi.org/10.13039/501100007287
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100000781
http://dx.doi.org/10.13039/501100002704
http://dx.doi.org/10.13039/501100014180
29844052
eng
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-76394-R
info:eu-repo/grantAgreement/EC/FP7/334763
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64556-R
closedAccess
American Association for the Advancement of Science