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

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-?B 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-?B pathway.

SUBMITTER: Kong S 

PROVIDER: S-EPMC4259264 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Kong Sinyi S   Thiruppathi Muthusamy M   Qiu Quan Q   Lin Zhenghong Z   Dong Hongxin H   Chini Eduardo N EN   Prabhakar Bellur S BS   Fang Deyu D  

Journal of immunology (Baltimore, Md. : 1950) 20141031 11

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  ...[more]

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