GEO series

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

GSE246799 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2024/06/04 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 24 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 24 samples: 8 × MBC, D14, vs 8 × BMPC, D14, vs 4 × Naive, vs 4 × GC, D14,Groups 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 GSE246799 in finder → Find more mouse RNA-seq 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 GSE246799_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1034627 and SRA study SRP469738. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38969872) ↗

Study design

8 × MBC, D14, vs 8 × BMPC, D14, vs 4 × Naive, vs 4 × GC, D14,

Supports a between-group comparison across 24 samples.

How we read this: 4 replicated groups read from 24 sample titles; they account for 24 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

GSM7877245 Naive, rep1 Naive,
GSM7877246 Naive, rep2 Naive,
GSM7877247 Naive, rep3 Naive,
GSM7877248 Naive, rep4 Naive,
GSM7877249 GC, D14, rep1 GC, D14,
GSM7877250 GC, D14, rep2 GC, D14,
GSM7877251 GC, D14, rep3 GC, D14,
GSM7877252 GC, D14, rep4 GC, D14,
GSM7877253 MBC, D14, rep1 MBC, D14,
GSM7877254 MBC, D14, rep2 MBC, D14,
GSM7877255 MBC, D14, rep3 MBC, D14,
GSM7877256 MBC, D14, rep4 MBC, D14,
GSM7877257 MBC, D14, rep5 MBC, D14,
GSM7877258 MBC, D14, rep6 MBC, D14,
GSM7877259 MBC, D14, rep7 MBC, D14,
GSM7877260 MBC, D14, rep8 MBC, D14,
GSM7877261 BMPC, D14, rep1 BMPC, D14,
GSM7877262 BMPC, D14, rep2 BMPC, D14,
GSM7877263 BMPC, D14, rep3 BMPC, D14,
GSM7877264 BMPC, D14, rep4 BMPC, D14,
GSM7877265 BMPC, D14, rep5 BMPC, D14,
GSM7877266 BMPC, D14, rep6 BMPC, D14,
GSM7877267 BMPC, D14, rep7 BMPC, D14,
GSM7877268 BMPC, D14, rep8 BMPC, D14,

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