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Series GSE173673 Query DataSets for GSE173673
Status Public on Aug 30, 2021
Title Transcriptional regulation of cell fate decisions in early B cell activation.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The cell fate decisions between plasmablasts (PBs), germinal center B cells (GCBCs) and non-GC-derived early memory B cells (eMBCs) during early B cell activation determine the outcome of the immune responses to pathogens and vaccines. To characterize these poorly understood lineage choices, we dissected the early B cell responses to T-dependent antigen in mice by single-cell RNA-sequencing. Early after immunization, a homogenous population of activated precursors (APs) gave rise to a transient wave of PBs, followed a day later by the emergence of the first GCBCs, with the transcriptomes of both rapidly diverging from that of APs. The majority of APs started to withdraw from the cell cycle very early on and gave rise to eMBCs, a developmental transition that involved limited transcriptional changes. These events were controlled by antigen availability that rapidly declined soon after immunization, and provision of antigen excess interfered with the cell cycle exit of APs and induced a new wave of PBs. Fate mapping experiments revealed a prominent contribution of eMBCs to the overall MBC pool. Generation of the earliest GCBCs was tightly controlled by the transcriptional repressor Bhlhe40 in the absence of which this population was increased in numbers. Bhlhe40 also restrained in a cell intrinsic fashion the response of T follicular helper (TFH) cells, a specialized T helper cell subset required to mount the GC response. In B cells, Bhlhe40 executed its function in the first days after immunization by selectively restricting the generation of the earliest GCBCs but not of eMBCs or PBs. Conditional Bhlhe40 inactivation confirmed cell-autonomous functions of Bhlhe40 in both GCBCs and TFH cells, while the GC phenotype was further enhanced upon loss of Bhlhe40 in both cell types. This negative regulation of the GC reaction by Bhlhe40 was of crucial importance, as Bhlhe40-deficient mice with progressing age succumbed to a B cell lymphoma characterized by the accumulation of monoclonal GCBCs-like cells and polyclonal TFH cells in various tissues.
 
Overall design 23 bulk RNA-seq samples, 3 single cell RNA-seq, 10 bulk RNA-seq, 2 ChIP-seq
 
Contributor(s) Rauschmeier R, Reinhardt A, Gustafsson C, Glaros V, Artemov AV, Taneja R, Adameyko I, Månsson R, Busslinger M, Kreslavsky T, Ols S, Emmanouilidi A, You Y, Mirabello C, Björklund Å, Perez L, King N, Angeletti D, Loré K
Citation(s) 34525339, 37069502
Submission date Apr 30, 2021
Last update date May 12, 2023
Contact name Maria Fischer
Organization name Research Institute of Molecular Pathology
Lab Busslinger Group
Street address Campus-Vienna-Biocenter 1
City Vienna
ZIP/Postal code 1030
Country Austria
 
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21626 NextSeq 550 (Mus musculus)
Samples (38)
GSM5273496 58628_RNA-seq WT DZ GC B cells from mixed chimeras immunized with SRBC
GSM5273497 58629_RNA-seq WT LZ GC B cells from mixed chimeras immunized with SRBC
GSM5273498 58630_RNA-seq Bhlhe40-/- DZ GC B cells from mixed chimeras immunized with SRBC
Relations
BioProject PRJNA726572
SRA SRP318045

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE173673_RAW.tar 6.3 Gb (http)(custom) TAR (of BW, H5, TXT)
GSE173673_d2.seurat.rds.gz 689.9 Mb (ftp)(http) RDS
GSE173673_d2_GSE173673_d3_wt.seurat.rds.gz 801.5 Mb (ftp)(http) RDS
GSE173673_d2_GSE173673_d3_wtko.seurat.rds.gz 946.6 Mb (ftp)(http) RDS
GSE173673_d3_wt.seurat.rds.gz 203.4 Mb (ftp)(http) RDS
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record
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