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Series GSE121025 Query DataSets for GSE121025
Status Public on Jun 16, 2019
Title Transcriptional profiling of Ampk-deficient B cells during terminal differentiation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 5’-AMP-Activated Protein Kinase (Ampk) is an energy gatekeeper that responds to decreases in available ATP by inhibiting energy-consuming processes like protein synthesis and promoting energy-generating processes like glucose uptake. Recently, our lab showed that Lkb1, a previously unstudied kinase in B cell immunology and the main upstream kinase of Ampk, had a critical and unexpected role in B cell activation and germinal center formation. In T cells knockout of the downstream target Ampk, only partially phenocopies Lkb1 deletion, so we sought to determine whether the role of Lkb1 in B cells depends on Ampk. We find Ampk is activated upon B cell stimulation in vitro. Surprisingly, however, Ampk activation occurs in the absence of energetic stress, and B cells continue to grow and divide despite Ampk activity. We performed an IP-MS substrate screen to identify Ampk targets and only identified a limited repertoire of canonical targets, and many non-canonical targets. Despite activation of Ampk and the major role of Lkb1 in B cell activation, B cell specific deletion of Ampk does not significantly affect B cell activation, differentiation, carbon handling, gene expression, or humoral immune responses. The only major effect of Ampk loss was accelerated downregulation of IgD during stimulation, which was preceded by downregulation of the IgD regulator Zfp318. Early activation of Ampk by pharmacological means also has little impact on B cell function, although treatment with the biguanide Phenformin critically impairs germinal center formation and class switch recombination in vivo, but does not significantly impair antigen-specific antibody responses. Combined, our results suggest an unexpected and unexplained activation of Ampk in B cells.
Overall design Bulk RNA-sequencing of CD43- sorted CD19-Cre+/-Prkaa1-/- (KO) and CD19-Cre+/-Prkaa1+/+ (WT) splenic naïve B cells (n = 3 each genotype), stimulated using CD40L + IL4 in vitro to terminal differentiation over 5 days (n = 3 each genotype at 5 timepoints plus naive, 36 samples total).
Contributor(s) Ahsan FM, Waters LR, Teitell MA
Citation(s) 31160601
Submission date Oct 09, 2018
Last update date Jun 16, 2019
Contact name Fasih Mubtasim Ahsan
Organization name UCLA
Department Pathology and Laboratory Medicine
Lab Teitell Lab, MRL 4-567
Street address 675 Charles E. Young Drive South
City Los Angeles
State/province CA
ZIP/Postal code 90095-1732
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (36)
GSM3424067 WT-D0 1
GSM3424068 KO-D0 1
GSM3424069 WT-D1 1
BioProject PRJNA495374
SRA SRP164756

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE121025_GEO_rawcountmatrix.csv.gz 3.6 Mb (ftp)(http) CSV
GSE121025_GEO_samplemetadata.csv.gz 2.5 Kb (ftp)(http) CSV
GSE121025_RAW.tar 73.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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