biostudies-literatureKong SNIDDK NIH HHSNIAID NIH HHSNIAMS NIH HHS5515-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC4259264biostudies-literatureUnknown193(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 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.Journal of immunology (Baltimore, Md. : 1950)DBC1 is a suppressor of B cell activation by negatively regulating alternative NF-κB transcriptional activity.PMC4259264R01 DK084055R01 AI079056R01 AI108634AI108634AI079056R56 AI079056DK-084055R01 AR066634AR066634Thiruppathi MDong HFang DQiu QKong SLin ZChini ENPrabhakar BSfalseDBC1 is a suppressor of B cell activation by negatively regulating alternative NF-κB transcriptional activity.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.2014-01-01T00:00:00Z2014 Dec2024-12-04T08:17:07.459Z2019-03-27T01:41:16ZS-EPMC42592642536217910.4049/jimmunol.1401798