GEO series

Somatic deficiency of human E3 ubiquitin ligase CBL in leukocytes Impairs B cell but not T cell development and function

GSE307131 Homo sapiens (human) RNA-seq (gene expression) 10 samples Submitted 2025/11/10 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 10 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: Homo sapiens (human)
Samples: 10 samples: 10 samples, each with a distinct title — no replicated groupsGroups 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: Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and functionNature immunology · 2026

Summary (written by the submitters)

The casitas B lineage lymphoma (CBL) proto-oncogene promotes positive selection and antigen responses in murine T lymphocytes by ubiquitinating ZAP70. However, CBL and CBL-B are redundant for ubiquitination of SYK and regulation of B cell receptor (BCR) signaling in murine B cells. We studied lymphocyte development, maturation and function in patients with somatic homozygosity for CBL loss-of-function variants in leukocytes.

Read the full summary ↓

Surprisingly, human CBL is largely redundant for the development and function of human T cells. Conversely, CBL is critical for B cell development and function. Patients with somatic, hematopoietic CBL deficiency have a 10-fold increase in transitional B cells during childhood and are susceptible to bacterial infections. CBL deficiency impairs B cell maturation in a cell-intrinsic manner through reduced apoptosis and dysregulated BCR signaling, thereby reducing the proportions and numbers of memory B cells. Overall, our findings demonstrate that CBL deficiency has two major effects on human B cells. First, B-cell development in the bone marrow is altered at the immature stage, resulting in enhanced survival and differentiation of autoreactive B cell clones and impaired B cell tolerance, manifested as the production of autoantibodies. Second, the generation of antigen-specific B cells is impaired, thereby disrupting the establishment of adaptive immune memory. Thus, our study reveals the critical role of human CBL in B cells and its redundancy in T cells.

Published in

Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function

Vatovec T, Neehus AL, Jackson KJL et al. · Nature immunology 2026 · PMID 41540267 · doi:10.1038/s41590-025-02381-7

This dataset

Open GSE307131 in finder → Find more human 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 GSE307131_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 PRJNA1314633 and SRA study SRP616826. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41540267) ↗

Study design

10 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 10 sample titles: 10 distinct titles with little repetition. 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

GSM9217043 human CD34+-derived CD19+CD10+CD20dim B progenitors, AAVS1 KO, Day 21, biol rep 1, A
GSM9217044 human CD34+-derived CD19+CD10+CD20dim B progenitors, AAVS1 KO, Day 21, biol rep 1, B
GSM9217045 human CD34+-derived CD19+CD10+CD20dim B progenitors, AAVS1 KO, Day 21, biol rep 2, A
GSM9217046 human CD34+-derived CD19+CD10+CD20dim B progenitors, AAVS1 KO, Day 21, biol rep 2, B
GSM9217047 human CD34+-derived CD19+CD10+CD20dim B progenitors, CBL KO, Day 21, biol rep 1, A
GSM9217048 human CD34+-derived CD19+CD10+CD20dim B progenitors, CBL KO, Day 21, biol rep 1, B
GSM9217049 human CD34+-derived CD19+CD10+CD20dim B progenitors, CBL KO, Day 21, biol rep 2, A
GSM9217050 human CD34+-derived CD19+CD10+CD20dim B progenitors, CBL KO, Day 21, biol rep 2, B
GSM9217051 human CD34+-derived CD19+CD10+CD20dim B progenitors, PI3KGOF, Day 21, biol rep 1, A
GSM9217052 human CD34+-derived CD19+CD10+CD20dim B progenitors, PI3KGOF, Day 21, biol rep 1, B

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.