GEO series

Epigenetic recording of stimulation history reveals BLIMP1-BACH2 balance in determining memory B cell fate upon recall challenge (ATAC-Seq I)

GSE246797 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 15 samples Submitted 2024/06/04 Platform GPL24247

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 15 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Mus musculus (mouse)
Samples: 15 samples: 5 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Epigenetic recording of stimulation history reveals BLIMP1-BACH2 balance in determining memory B cell fate upon recall challengeNature immunology · 2024

Summary (written by the submitters)

Long-term humoral immunity is partly maintained by memory B cells (MBCs). MBCs can be recalled to produce antibody-producing plasma cells (PCs) or form secondary germinal centers (GCs). The former process underlies markedly increased antigen-specific antibodies seen in the secondary response, while the latter process allows continuous somatic hypermutation and affinity maturation.

Read the full summary ↓

MBC re-participation in the GC reaction is thought to be important for generating broadly neutralizing antibodies against highly mutating viruses such as influenza and HIV. However, how MBC recall is transcriptionally or epigenetically programmed to produce secondary PCs or GCs is not yet understood. Here we show that BACH2, a transcription factor required for GC formation and maintenance1,2, decreases across post-activation stages of B cells, from the naïve state to GC, memory, and the terminal PC state. In contrast, BLIMP-1, a transcription factor that promotes PC formation3,4 and is antagonistic to BACH2 (ref. 5), increases as B cells traverse the same course. The relative strength between BLIMP-1 and BACH2 progressively increases in favor of BLIMP-1 in GCs and MBCs through the primary response. MBCs of the isotype or subset identity that preferentially give rise to secondary GCs exhibit comparatively higher BACH2 but lower BLIMP-1 expression than those predisposed for PC formation. Using a tetracycline-controlled circuit implanted in MBCs, we show that skewing the BLIMP-1-BACH2 balance in favor of BACH2 markedly increases GC formation by otherwise PC-predisposed MBCs, whereas skewing the balance in favor of BLIMP-1 drives PC formation by GC-prone MBCs, indicating that the potential for GC re-participation or PC development rests in the relative strength of BLIMP-1 over BACH2 within individual MBCs. Underneath this relative BLIMP-1-over-BACH2 strength in naïve B cells, GCs, MBCs and PCs, we observe progressively increased accessibilities to chromatin loci that are specifically opened in PCs, particularly those that contain ISRE elements and are controlled by IRF-4. IRF-4 is universally upregulated in B cells when stimulated through the BCR, the CD40 receptor, or by innate stimuli. By analyzing time-stamped GC B cells, we demonstrate a progressive increase in chromatin accessibilities at PC-specific, IRF-4-controlled gene loci over time. Our results support a model of progressive IRF-4 imprinting in which the cumulative stimulation history of B cells is epigenetically recorded in an IRF-4-dependent manner, determines the relative strength between BLIMP-1 and BACH2 in individual MBCs, and thereby dictates their individual probabilities to develop into GCs or PCs upon re-stimulation.

Published in

Epigenetic recording of stimulation history reveals BLIMP1-BACH2 balance in determining memory B cell fate upon recall challenge

Shao W, Wang Y, Fang Q et al. · Nature immunology 2024 · PMID 38969872 · doi:10.1038/s41590-024-01900-2

This dataset

Open GSE246797 in finder → Find more mouse ChIP / ATAC / CUT&Tag datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE246797_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1034625 and SRA study SRP469749. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38969872) ↗

Study design

5 conditions, mostly in triplicate

Naïve, ATAC-seq, ×3 GC, ATAC-seq, ×3 YFP, ATAC-seq, ×3 RFP, ATAC-seq, ×3 PC, ATAC-seq, ×3

Supports a between-group comparison across 15 samples.

How we read this: 5 replicated groups read from 15 sample titles; they account for 15 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM7877221 Naïve, ATAC-seq, rep1 Naïve, ATAC-seq,
GSM7877222 Naïve, ATAC-seq, rep2 Naïve, ATAC-seq,
GSM7877223 Naïve, ATAC-seq, rep3 Naïve, ATAC-seq,
GSM7877224 GC, ATAC-seq, rep1 GC, ATAC-seq,
GSM7877225 GC, ATAC-seq, rep2 GC, ATAC-seq,
GSM7877226 GC, ATAC-seq, rep3 GC, ATAC-seq,
GSM7877227 YFP, ATAC-seq, rep1 YFP, ATAC-seq,
GSM7877228 YFP, ATAC-seq, rep2 YFP, ATAC-seq,
GSM7877229 YFP, ATAC-seq, rep3 YFP, ATAC-seq,
GSM7877230 RFP, ATAC-seq, rep1 RFP, ATAC-seq,
GSM7877231 RFP, ATAC-seq, rep2 RFP, ATAC-seq,
GSM7877232 RFP, ATAC-seq, rep3 RFP, ATAC-seq,
GSM7877233 PC, ATAC-seq, rep1 PC, ATAC-seq,
GSM7877234 PC, ATAC-seq, rep2 PC, ATAC-seq,
GSM7877235 PC, ATAC-seq, rep3 PC, ATAC-seq,

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