PXD035459

PXD035459 is an original dataset announced via ProteomeXchange.

Title	Multi-omics Analysis of naive B cells of patients harboring the C104R mutation in TACI
Description	Common variable immunodeficiency (CVID) is the most prevalent form of symptomatic primary immunodeficiency in humans. The genetic cause of CVID is still unknown in about 70% of cases. 10% of CVID patients carry heterozygous mutations in the tumor necrosis factor receptor superfamily member 13B gene (TNFRSF13B), encoding TACI. Mutations in TNFRSF13B alone may not be sufficient for the development of CVID, as 1% of the healthy population carry these mutations. The common hypothesis is that TACI mutations are not fully penetrant and additional factors contribute to the development of CVID. To determine these additional factors, we investigated the perturbations of transcription factor (TF) binding and the transcriptome profiles in unstimulated and CD40L/IL21-stimulated naïve B cells from CVID patients harboring the C104R mutation in TNFRSF13B and compared them to their healthy relatives with the same mutation. In addition, the proteome of stimulated naïve B cells was investigated. For functional validation, intracellular protein concentrations were measured by flow cytometry. Our analysis revealed 8% less accessible chromatin in unstimulated naïve B cells and 25 % less accessible chromatin in class-switched memory B cells from affected and unaffected TACI mutation carriers compared to healthy donors. The most enriched TF binding motifs in TACI mutation carriers involved members from the ETS, IRF and NF-B TF families. Validation experiments supported dysregulation of the NF-B and MAPK pathways. In steady state, naïve B cells had increased cell death pathways and reduced cell metabolism pathways; while after stimulation, enhanced immune responses and decreased cell survival was detected. Using a multi-omics approach, our findings provide valuable insights into the impaired biology of naïve B cells from TACI mutation carriers.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:32:51.219.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matteo Pecoraro
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 05:38:02	ID requested
1	2022-10-14 10:04:16	announced
⏵ 2	2023-11-14 08:32:52	announced	2023-11-14: Updated project metadata.

Ramirez N, Posadas-Cantera S, Langer N, de Oteyza ACG, Proietti M, Keller B, Zhao F, Gernedl V, Pecoraro M, Eibel H, Warnatz K, Ballestar E, Geiger R, Bossen C, Grimbacher B, ve B cells of patients harboring the C104R mutation in TACI. Front Immunol, 13():938240(2022) [pubmed]

submitter keyword: ATAC-seq, CD40L stimulation, DNA accessibility, proteomics,TACI, TNFRSF13B, transcription factor, CVID, naïve B cells, NF-B, RNA-seq

Bodo Grimbacher
contact affiliation	Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg. Breisacher Strae 115, 79106 Freiburg, Germany.
contact email	bodo.grimbacher@uniklinik-freiburg.de
lab head
Matteo Pecoraro
contact affiliation	Institute for Research in Biomedicine, Via Vincenzo Vela 6 - CH-6500 Bellinzona
contact email	matteo.pecoraro@irb.usi.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/10/PXD035459

PRIDE project URI

• PRIDE
  1. PXD035459
     1. Label: PRIDE project
     2. Name: Multi-omics Analysis of naive B cells of patients harboring the C104R mutation in TACI