DBC1 is a suppressor of B cell activation by negatively regulating alternative NF-κB transcriptional activity

Sinyi Kong, Muthusamy Thiruppathi, Quan Qiu, Zhenghong Lin, Hongxin Dong, Eduardo N. Chini, Bellur S. Prabhakar, Deyu Fang

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5515-5524
Number of pages10
JournalJournal of Immunology
Volume193
Issue number11
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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