期刊
CELLULAR IMMUNOLOGY
卷 294, 期 1, 页码 1-8出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2015.01.010
关键词
BRD4; Germinal center B cells; Antibody responses; Bcl6
Germinal center (GC) reaction is a T cell-dependent process in which activated B cells undergo clonal expansion and functional maturation to produce high affinity antibodies and differentiate into memory B cells(1). Here we demonstrate a new role of bromodomain and extraterminal domain (BET) protein BRD4 in GC B cell development. We found that during B cell differentiation stage there was an elevated expression of BRD4 in GC B cells and inhibition of BRD4 by small molecule inhibitors led to the suppression of GC formation and correspondent antibody responses in a Td antigen immunization model. At the molecular level, we found that the effects of BRD4 in primary GC B cell differentiation and B cell lymphoma were mediated through the impaired phosphorylation and translocation of NF-kappa Bp65 and further down-regulation of B-cell lymphoma 6 (Bcl6) expression. Thus this study reveals a novel function of BRD4 in controlling the GC B cell development pathway. Published by Elsevier Inc.
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