{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kong S"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","NIAMS NIH HHS"],"pagination":["5515-24"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4259264"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["193(11)"],"pubmed_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."],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["DBC1 is a suppressor of B cell activation by negatively regulating alternative NF-κB transcriptional activity."],"pmcid":["PMC4259264"],"funding_grant_id":["R01 DK084055","R01 AI079056","R01 AI108634","AI108634","AI079056","R56 AI079056","DK-084055","R01 AR066634","AR066634"],"pubmed_authors":["Thiruppathi M","Dong H","Fang D","Qiu Q","Kong S","Lin Z","Chini EN","Prabhakar BS"],"additional_accession":[]},"is_claimable":false,"name":"DBC1 is a suppressor of B cell activation by negatively regulating alternative NF-κB transcriptional activity.","description":"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.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Dec","modification":"2024-12-04T08:17:07.459Z","creation":"2019-03-27T01:41:16Z"},"accession":"S-EPMC4259264","cross_references":{"pubmed":["25362179"],"doi":["10.4049/jimmunol.1401798"]}}