TY - JOUR
T1 - DBC1 is a suppressor of B cell activation by negatively regulating alternative NF-κB transcriptional activity
AU - Kong, Sinyi
AU - Thiruppathi, Muthusamy
AU - Qiu, Quan
AU - Lin, Zhenghong
AU - Dong, Hongxin
AU - Chini, Eduardo N.
AU - Prabhakar, Bellur S.
AU - Fang, Deyu
N1 - Publisher Copyright:
Copyright © 2014 by The American Association of Immunologists, Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.1401798
DO - 10.4049/jimmunol.1401798
M3 - Article
C2 - 25362179
AN - SCOPUS:84912553264
SN - 0022-1767
VL - 193
SP - 5515
EP - 5524
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -