Modulation of B cell activation threshold mediated by BCR/CD40 costimulation by targeting Cbl-b for ubiquitination

Na Tang; Lifen Yang; Dongdong Li; Rushi Liu; Jian Zhang

doi:10.1016/j.bbrep.2019.100641

Back

Modulation of B cell activation threshold mediated by BCR/CD40 costimulation by targeting Cbl-b for ubiquitination

Journal article

Open access

Peer reviewed

Modulation of B cell activation threshold mediated by BCR/CD40 costimulation by targeting Cbl-b for ubiquitination

Na Tang, Lifen Yang, Dongdong Li, Rushi Liu and Jian Zhang

Biochemistry and biophysics reports, Vol.18, pp.100641-100641

07/2019

DOI: 10.1016/j.bbrep.2019.100641

PMCID: PMC6487278

PMID: 31061898

Files and links (1)

url

https://doi.org/10.1016/j.bbrep.2019.100641View

Published (Version of record) Open Access

Abstract

It has been shown that CD40 is required for optimal B cell activation. Casitas-B-lineage lymphoma-b (Cbl-b), a RING finger E3 ubiquitin ligase, inhibits B cell activation. In this report, we demonstrate that CD40 stimulation markedly enhances IgM-induced B cell proliferation in wild-type (WT) mice, whereas this cell proliferation was reduced in CD40-deficient ( ) mice. Interestingly, CD40 ligation strongly augments IgM-induced Cbl-b ubiquitination and degradation in primary mouse B cells, which closely correlates with their proliferation capacity. Cbl-b deficiency uncouples BCR-induced B cell proliferation from CD40 costimulation. Our results indicate that Cbl-b negatively regulates costimulation of BCR and CD40, possibly by setting the threshold for B cell activation via controlling Cbl-b expression.

Details

Title: Subtitle: Modulation of B cell activation threshold mediated by BCR/CD40 costimulation by targeting Cbl-b for ubiquitination
Creators: Na Tang - Department of Pathology, University of Iowa, 25 S. Grand Ave., Iowa City, IA, 52242, USA
Lifen Yang - University of Chicago
Dongdong Li - Department of Orthopedics, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL, 60612, USA
Rushi Liu - Laboratory of Medical Molecular and Immunological Diagnostics (LMMID), Hunan Normal University, 371 Tongzipo Road, Changsha, Hunan, 410013, PR China
Jian Zhang - University of Iowa, Pathology
Resource Type: Journal article
Publication Details: Biochemistry and biophysics reports, Vol.18, pp.100641-100641
DOI: 10.1016/j.bbrep.2019.100641
PMID: 31061898
PMCID: PMC6487278
NLM abbreviation: Biochem Biophys Rep
ISSN: 2405-5808
eISSN: 2405-5808
Grant note: R01 AI123253 / NIAID NIH HHS R01 AI090901 / NIAID NIH HHS R01 AR049775 / NIAMS NIH HHS P30 CA086862 / NCI NIH HHS K02 AR049047 / NIAMS NIH HHS
Language: English
Date published: 07/2019
Academic Unit: Pathology
Record Identifier: 9984195953602771

Metrics

6 Record Views

6 Times Cited - Web of Science