| First Author | Zhang P | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 2 | Pages | 726-36 |
| PubMed ID | 23752615 | Mgi Jnum | J:204823 |
| Mgi Id | MGI:5543528 | Doi | 10.4049/jimmunol.1202134 |
| Citation | Zhang P, et al. (2013) Notch-regulated periphery B cell differentiation involves suppression of E protein function. J Immunol 191(2):726-36 |
| abstractText | 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. |
