R-Ras2 is required for germinal center formation to aid B cells during energetically demanding processes.

Science Signaling
Pilar MendozaBalbino Alarcón

Abstract

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 cel...Continue Reading

References

Apr 1, 1990·Molecular and Cellular Biology·G T DrivasP D'Eustachio
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·A M ChanS A Aaronson
Jun 1, 1994·Molecular and Cellular Biology·S M GrahamC J Der
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B VanhaesebroeckM D Waterfield
Jan 31, 1998·The EMBO Journal·B M IritaniR M Perlmutter
Apr 25, 2000·The Journal of Biological Chemistry·Y OhbaM Matsuda
Mar 16, 2002·Nature Immunology·Tien-An Yang ShihMichel C Nussenzweig
Jul 20, 2002·Science·Klaus OkkenhaugBart Vanhaesebroeck
Apr 2, 2003·Nature Reviews. Immunology·Klaus Okkenhaug, Bart Vanhaesebroeck
Oct 18, 2003·Science·Marita J WalmsleyVictor L J Tybulewicz
May 15, 2004·Molecular and Cellular Biology·Pablo Rodriguez-VicianaFrank McCormick
Sep 16, 2004·Science's STKE : Signal Transduction Knowledge Environment·John Colicelli
Aug 23, 2005·Immunity·Yoshimasa TakahashiToshitada Takemori
Sep 17, 2008·Oncogene·L Zhao, P K Vogt
Feb 27, 2009·The Journal of Biological Chemistry·Ahmed EssaghirJean-Baptiste Demoulin
Mar 11, 2009·The Journal of Experimental Medicine·Masaki HikidaTomohiro Kurosaki
Jun 30, 2009·Nature Immunology·Pilar DelgadoBalbino Alarcón
Aug 21, 2009·Molecular Biology of the Cell·Fernando Calvo, Piero Crespo
Oct 16, 2009·Annual Review of Immunology·Tomohiro KurosakiYoshihiro Baba
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yuichi AibaTomohiro Kurosaki
Aug 24, 2010·Immunological Reviews·Markus WernerHassan Jumaa
Jul 23, 2011·Genes & Cancer·Esther Castellano, Eugenio Santos
Dec 7, 2011·Biochimica Et Biophysica Acta·Daniel F Bogenhagen
Dec 29, 2011·Current Pharmaceutical Biotechnology·J Chesney, S Telang
Jan 10, 2012·Annual Review of Immunology·Gabriel D Victora, Michel C Nussenzweig
Jan 25, 2012·The Journal of Cell Biology·Ana Maria RojasAlfonso Valencia
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Jun 13, 2012·Cold Spring Harbor Perspectives in Biology·Patrick S Ward, Craig B Thompson
Jul 14, 2012·Small GTPases·Balbino Alarcón, Nuria Martínez-Martín
Nov 28, 2012·Frontiers in Immunology·Nils Y Lycke, Mats Bemark
Feb 15, 2013·Immunological Reviews·Roybel R Ramiscal, Carola G Vinuesa
Apr 23, 2013·Immunity·Erika L Pearce, Edward J Pearce
Jul 16, 2013·Cell Death and Differentiation·I MartinsG Kroemer

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Citations

Jul 22, 2019·The Journal of Experimental Medicine·Ana Martínez-RiañoBalbino Alarcon
Jan 4, 2019·Genes & Development·Mark R BoothbyJames W Thomas
Mar 7, 2020·Experimental & Molecular Medicine·Seung-Chul Choi, Laurence Morel
Jun 11, 2021·The American Journal of Pathology·Shannon M Weber, Steven L Carroll
Jun 25, 2021·Frontiers in Immunology·Iwan G A Raza, Alexander J Clarke

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