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| Status |
Public on Apr 25, 2018 |
| Title |
R-Ras2 is required for germinal center formation to aid B cells during energetically demanding processes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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 cells clonal expansion, immunoglobulin class switching, and affinity maturation. This process, known as the GC response, is an energetically demanding process that requires metabolic reprogramming of B cells. Here, 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 increase 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 suggests that R-Ras2 may also regulate metabolism in B cell malignancies.
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| Overall design |
We aimed to characterize differences in mRNA expression between germinal center B cells FACS sorted from wild type mice and germinal center B cells FACS sorted from RRas2-deficient mice. To generate germinal center B cells, all mice were immunized 7 days earlier by administration of sheep red blood cells by the intraperitoneal route.
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| Contributor(s) |
Mendoza P, Martínez-Martín N, Bovolenta ER, Reyes-Garau D, Hernansanz-Agustín P, Delgado P, Diaz-Muñoz MD, Oeste CL, Fernández-Pisonero I, Castellano E, Martínez-Ruiz A, Alonso-Lopez D, Santos E, Bustelo XR, Kurosaki T, Alarcón B |
| Citation(s) |
29844052 |
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| Submission date |
Apr 24, 2018 |
| Last update date |
Jul 25, 2018 |
| Contact name |
Balbino Alarcon |
| E-mail(s) |
balarcon@cbm.csic.es
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| Phone |
+34 911964555
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| Organization name |
Centro de Biologia Molecular Severo Ochoa
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| Street address |
Nicolas Cabrera 1
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| City |
Madrid |
| State/province |
Madrid |
| ZIP/Postal code |
28049 |
| Country |
Spain |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (7)
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| GSM3109404 |
WT GC cells, biological replicate 4 |
| GSM3109405 |
RRas2-deficient GC cells, biological replicate 1 |
| GSM3109406 |
RRas2-deficient GC cells, biological replicate 2 |
| GSM3109407 |
RRas2-deficient GC cells, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA453195 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113599_RAW.tar |
61.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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