PXD040978-1

PXD040978 is an original dataset announced via ProteomeXchange.

Title	The Ubiquitin Ligase Itch Skews Light Zone Selection in Germinal Centers
Description	Ig diversification occurs in peripheral lymphoid organs after establishment of central tolerance during B cell development. In germinal centers (GCs), somatic hypermutation of Ig genes occurs in dark zones, followed by selection of mutated clones in light zones (LZs). This generates high-affinity Ig receptors to pathogens but can also produce autoreactive Ig receptors, which are removed by selection mechanisms that are incompletely understood. The ubiquitin ligase Itch prevents the emergence of autoimmune disease and autoantibodies in humans and mice, and patients lacking Itch develop potentially fatal autoimmune diseases; yet, how Itch regulates GC B cells is not well understood. By studying Itch-deficient mice, we have recently shown that Itch directly limits the magnitude of GC responses. Proteomic profiling of GC B cells uncovered that Itch-deficient cells exhibit high mTORC1 and Myc activity, hallmarks of positive selection. Bone marrow chimera and adoptive transfer experiments revealed that B cell Itch restricts noncycling LZ cells. These results support, t our knowledge, a novel role for Itch in skewing selection of GC B cells to restrict LZ accumulation and shape GC-derived humoral immunity. Determining how B cells integrate cues within GCs to navigate through LZs and dark zones will aid in understanding how autoreactive clones emerge from GCs in people with autoimmune disease.
HostingRepository	PRIDE
AnnounceDate	2024-11-12
AnnouncementXML	Submission_2024-11-12_07:21:01.388.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-20 08:21:45	ID requested
⏵ 1	2024-11-12 07:21:02	announced

10.4049/jimmunol.2200824;

Renshaw L, Kim P, Crici M, Fazelinia H, Spruce L, Oliver P, Moser E, The Ubiquitin Ligase Itch Skews Light Zone Selection in Germinal Centers. J Immunol, 210(10):1473-1481(2023) [pubmed]

submitter keyword: b-cell,germinal center, autoimmunity, ubiquitin ligase

Emily Moser, PhD
contact affiliation	University of Florida, Gainesville, FL. USA
contact email	emily.moser@medicine.ufl.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
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/2024/11/PXD040978

PRIDE project URI

• PRIDE
  1. PXD040978
     1. Label: PRIDE project
     2. Name: The Ubiquitin Ligase Itch Skews Light Zone Selection in Germinal Centers