DBC1 is a Suppressor of B Cell Activation by Negatively Regulating Alternative NF-κB Transcriptional Activity

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2014 Nov 2

PMID 25362179

Citations 5

Authors

Sinyi Kong

Muthusamy Thiruppathi

Quan Qiu

Zhenghong Lin

Hongxin Dong

Eduardo N Chini

Bellur S Prabhakar

Deyu Fang

Affiliations

Soon will be listed here.

Abstract

CD40 and BAFFR signaling play important roles in B cell proliferation and Ig production. In this study, we found that B cells from mice with deletion of Dbc1 gene (Dbc1(-/-)) show elevated proliferation, and IgG1 and IgA production upon in vitro CD40 and BAFF, but not BCR and LPS stimulation, indicating that DBC1 inhibits CD40/BAFF-mediated B cell activation in a cell-intrinsic manner. Microarray analysis and chromatin immunoprecipitation experiments reveal that DBC1 inhibits B cell function by selectively suppressing the transcriptional activity of alternative NF-κB members RelB and p52 upon CD40 stimulation. As a result, when immunized with nitrophenylated-keyhole limpet hemocyanin, Dbc1(-/-) mice produce significantly increased levels of germinal center B cells, plasma cells, and Ag-specific Ig. Finally, loss of DBC1 in mice leads to higher susceptibility to experimental autoimmune myasthenia gravis. Our study identifies DBC1 as a novel regulator of B cell activation by suppressing the alternative NF-κB pathway.

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