Antigen-Independent, Autonomous B-cell Receptor Signalling in Diffuse Large B-cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) comprises two major cell-of-origin subtypes, germinal center B-cell (GCB) type and activated B-cell (ABC) type. ABC-DLBCL is characterized by chronic active B-cell receptor (BCR) signalling and NFκB activation, which is explained by activating mutations of the BCR signalling cascade in a minority of cases. We here demonstrate that autonomous BCR signalling, akin to its essential pathogenetic role in chronic lymphocytic leukemia (CLL), can explain chronic active BCR signalling in DLBCL. We show that 13 of 18 tested DLBCL-derived BCR induced spontaneous calcium flux in murine triple knock-out pre-B cells10 in the absence of antigenic stimulation or external BCR crosslinking. Autonomous BCR signalling was associated with IgM isotype, dependent on somatic BCR mutations, and largely restricted to non-GCB DLBCL. Autonomous BCR signaling represents a novel immunological driver mechanism originating from individual BCR sequences and adds a new dimension to ..., Cell lines and biopsies
Fresh-frozen biopsies of histologically confirmed DLBCL samples were identified in the pathology archive at Leiden University Medical Center (LUMC). The study was approved by the Scientific Review Committee of the LUMC Dept of Hematology under an applicable waiver of consent by the LUMC Ethical Committee (B16.048).

Genetic analyses
Whole exome sequencing (WES) was performed on fragmented DNA with the SureSelect Human All Exon V7 kit (Agilent) capture on the HiSeq2000 (Illumina) platform to an average coverage of 50x. For the variant calling analysis, FASTQ files were processed using the Sarek workflow v2.7 and aligned to the human reference genome GRCh38 using the Burrows-Wheeler Algorithm (BWA) v0.7.17. 35,36 Duplicated mapped reads were marked, local realignment of regions flanking indels, and recalibration of base quality scores were performed to obtain more accurate bases according to the Genome Analysis ToolKit (GATK) best practices version v4.1.7.0. 37 S..., , , # Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL

[https://doi.org/10.5061/dryad.612jm647m](https://doi.org/10.5061/dryad.612jm647m)

This dataset contains raw whole-exome sequencing (WES) data in paired-end FASTQ format for 15 patient samples diagnosed with diffuse large B-cell lymphoma (DLBCL). These data were generated to support downstream analyses, including variant calling, copy number variation (CNV) detection, structural variant identification, and molecular classification using the LymphGen algorithm.

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**Principal Investigator Contact Information**

Name: Hendrik Veelken

Institution: Leiden University Medical Center

Email: [[e-mail]](mailto:[e-mail])

**Alternate Contact Information**

Name: Cornelis van Bergen

Institution: Leiden University Medical Center

Email: [[e-mail]](mailto:[e-mail])

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## Description of the Data and File Structure

### File Format and Structure

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