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The murine meninges is a resilient B cell lymphopoietic reservoir conferring protection against infections

GSE297581 Mus musculus (mouse) RNA-seq (gene expression) 32 samples Submitted 2025/11/06 Platform GPL34290
At a glance

RNA-seq (gene expression) · mouse · 32 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
32 samples: 8 conditions, mostly with about 4 replicates eachGroups 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.
Summary (written by the submitters)
It is now recognised that under homeostasis the dura meninges host a wide array of resident early haematopoietic precursors including those responsible for de novo B cell lymphopoiesis. The vascular connections between the skull bone marrow in the calvaria and the underlying meningeal layers provide an anatomical bridge connecting these two structures, and most of the early precursor populations are likely to originate from the calvaria before seeding the dura meninges.
Read the full summary ↓
However, the impact of chronic, non-sterile challenges such as infections on these resident precursor populations remains to be determined. Furthermore, it is unclear whether the mechanisms providing local tolerance to infection result in the same outputs as those generated in conventional lymphoid organs such as the spleen. Trypanosoma brucei parasites, the causative agents of sleeping sickness, successfully colonise a myriad of tissues during the chronic stages of the infection, including the central nervous system (CNS) borders and the brain parenchyma. In the periphery, T. brucei infection results in severe B cell lymphopenia, including NK- and neutrophil mediated killing of conventional B-2 B cells in the spleen, compromising subsequent humoral responses necessary to control the infection. This begs the question of whether alternative tissue sites are also capable of supporting B cell lymphopoiesis when canonical lymphoid tissues such as the bone marrow and the spleen are severely compromised. We recently identified that the dura meninges acquire properties typically associated with ectopic lymphoid clusters resulting in the generation of high affinity antibodies during the chronic stages of the infection. Critically, the presence of these dura-associated lymphoid tissues under homeostasis was interdependently reported in mice and humans, highlighting conservation of these immunological hubs across species. In this study, we asked whether chronic T. brucei infection also disrupts meningeal B cell development, as it is recognised to take place in bona fide lymphopoietic organs such as the bone marrow and the spleen in response to T. brucei infection resulting in B cell lymphopenia. Thorough a combination of approaches, we show that the dura meninges support B cell lymphopoiesis when peripheral B cell lymphopoiesis is impaired. Mechanistically, we report that meningeal stroma, in particular signals derived from fibroblasts, endothelial, and sensory neurons provide environmental cues for the survival and development of these cells locally in a process dependent of IL-7 and STAT5 signalling resulting in sustained B cell replication capacity in this anatomical compartment. Critically, we show that the repertoire of B cells developing in the dura meninges undergo extensive clonal selection that is distinct from those found in the spleen. These B cells predominantly express various members of the Ighv1 family, including Ighv1-15, Ighv1-26, and Ighv1-76, that we proposed to be polyreactive and able to recognise a wide range of CNS antigens with various degrees of specificity, providing further evidence of tissue-specific B cell responses operating at the CNS borders. Lastly, through adoptive transfer experiments, we demonstrate that the B cells located in the meninges during infection, but not those from the spleen, protect B cell-deficient mice from infection for a longer period and are able to produce anti-T. brucei IgG. Collectively, our data demonstrate, for the first time, that the dura meninges independently support the development and selection of a a distinct reservoir of B cells when peripheral lymphopoietic organs are compromised, highlighting the meninges as a critical source of humoral responses against pathogens that highjack the peripheral immune system to promote chronicity.
This dataset
Open GSE297581 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 GSE297581_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 PRJNA1265219 and SRA study SRP586358. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, mostly with about 4 replicates each
Femur bone marrow naïve ×4 Femur bone marrow infected ×4 Skull bone marrow naïve ×4 Skull bone marrow infected ×4 Spleen naïve ×4 Spleen infected ×4 Meninges naïve ×4 Meninges infected ×4

Supports a between-group comparison across 32 samples.

How we read this: 8 replicated groups read from 32 sample titles; they account for 32 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
Datasets on a similar topic

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