کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2166951 | 1092295 | 2015 | 8 صفحه PDF | دانلود رایگان |
• Brd4 inhibition suppresses the GC B cell development and antibody responses.
• Bcl6 expression is down-regulated by Brd4 inhibition.
• Brd4 involves in the regulation of NF-κB pathway activity.
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-κBp65 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.
Journal: Cellular Immunology - Volume 294, Issue 1, March 2015, Pages 1–8