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Dynamic regulation of somatic hypermutation in germinal centers enables rapid B cell clonal expansion without loss of affinity

GSE285185 Mus musculus (mouse) RNA-seq (gene expression) 17 samples Submitted 2025/03/17 Platform GPL34475Platform GPL30172
At a glance

RNA-seq (gene expression) · mouse · 17 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
17 samples: 5 conditions, mostly in duplicateGroups 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
Transient silencing of hypermutation preserves B cell affinity during clonal burstingNature · 2025
Summary (written by the submitters)
In the course of antibody affinity maturation, germinal center (GC) B cells mutate their immunoglobulin (Ig) heavy and light chain genes in a process known as somatic hypermutation (SHM). Panels of mutant B cells with different binding affinities for antigen are then selected in Darwinian fashion, leading to a progressive increase in affinity among the population.
Read the full summary ↓
As with any Darwinian process, rare gain-of-fitness mutations must be identified while common loss-of-fitness mutations are avoided. Progressive acquisition of mutations therefore poses a risk during large proliferative bursts, when GC B cells go through several cell cycles in the absence of affinity-based selection. Using a combination of in vivo mouse experiments and mathematical modeling, we show that GCs achieve this balance by strongly suppressing SHM during clonal burst-type expansion, so that a large fraction of the progeny generated during such bursts do not deviate from their ancestral genotype. Intravital imaging and image-based cell sorting of a new CyclinE(A)/cyclin-dependent kinase 2 (CDK2) reporter mouse strain showed that B cells actively undergoing proliferative bursts lack the transient CDK2low “G0-like” phase of the cell cycle in which SHM takes place. We propose a model in which inertially cycling B cells largely delay SHM until the G0-like phase that follows their final round of division in the DZ, thus maintaining affinity as they clonally expand in the absence of selection.
Published in
Transient silencing of hypermutation preserves B cell affinity during clonal bursting
Pae J, Schwan N, Ottino-Loffler B et al. · Nature 2025 · PMID 40108454 · doi:10.1038/s41586-025-08687-8
This dataset
Open GSE285185 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 GSE285185_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 PRJNA1201770 and SRA study SRP553239. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40108454) ↗
Study design
5 conditions, mostly in duplicate
Fig2a_HTO_JP ×2 Fig2a_VDJ_JP ×2 Fig2g_GEX_JP ×2 Fig2g_HTO_JP ×2 Fig2g_VDJ_JP ×2 Fig2a_GEX_JP ×1 Fig4_GEX_JP0076C ×1 Fig4_HTO_JP0076C ×1 +4 more

Supports a between-group comparison across 10 samples.

How we read this: 5 replicated groups read from 17 sample titles; they account for 10 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
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