期刊
JOURNAL OF IMMUNOLOGY
卷 191, 期 2, 页码 726-736出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1202134
关键词
-
类别
资金
- National Institutes of Health [AI56129]
- Lew and Myra Chair in Biomedical Research
Notch signaling pathway plays important roles in promoting the generation of marginal zone (MZ) B cells at the expense of follicular (FO) B cells during periphery B cell maturation, but the underlying molecular mechanisms are not well understood. We hypothesize that Notch favors the generation of MZ B cells by downregulating E protein activity. In this study, we demonstrated that expression of Id2 and ankyrin-repeat SOCS box-containing protein 2 was elevated in MZ B cells and by Notch signaling. Id2 inhibits the DNA binding activity of E proteins, whereas ankyrin-repeat SOCS box-containing protein 2 facilitates E protein ubiquitination. Next, we examined the phenotypes of splenic B cells in mice expressing constitutively active Notch1 and/or two gain-of-function mutants of E proteins that counteract Id2-mediated inhibition or Notch-induced degradation. We found that upregulation of E proteins promoted the formation of FO B cells, whereas it suppressed the maturation of MZ B cells. In contrast, excessive amounts of Notch1 stimulated the differentiation of MZ B cells and inhibited the production of FO B cells. More interestingly, the effects of Notch1 were reversed by gain of E protein function. Furthermore, high levels of Bcl-6 expression in FO B cells was shown to be diminished by Notch signaling and restored by E proteins. In addition, E proteins facilitated and Notch hindered the differentiation of transitional B cells. Taken together, it appears that Notch regulates peripheral B cell differentiation, at least in part, through opposing E protein function. The Journal of Immunology, 2013, 191: 726-736.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据