生发中心
加压器
生物
细胞生物学
抑制因子
BCL6公司
转录因子
炎症
效应器
表型
B细胞
免疫学
遗传学
抗体
基因
作者
Chuanxin Huang,Katerina Hatzi,Ari Melnick
摘要
The transcriptional repressor Bcl-6 operates in many hematopoietic lineages. Melnick and colleagues show that Bcl-6 with a mutant BTB corepressor interaction domain selectively impairs B cell effector function. The transcription factor Bcl-6 orchestrates germinal center (GC) reactions through its actions in B cells and T cells and regulates inflammatory signaling in macrophages. Here we found that genetic replacement with mutated Bcl6 encoding Bcl-6 that cannot bind corepressors to its BTB domain resulted in disruption of the formation of GCs and affinity maturation of immunoglobulins due to a defect in the proliferation and survival of B cells. In contrast, loss of function of the BTB domain had no effect on the differentiation and function of follicular helper T cells or that of other helper T cell subsets. Bcl6-null mice had a lethal inflammatory phenotype, whereas mice with a mutant BTB domain had normal healthy lives with no inflammation. The repression of inflammatory responses by Bcl-6 in macrophages was accordingly independent of the repressor function of the BTB domain. Bcl-6 thus mediates its actions through lineage-specific biochemical functions.
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