| First Author | Hampel F | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 24 | Pages | 6321-31 |
| PubMed ID | 21795747 | Mgi Jnum | J:179036 |
| Mgi Id | MGI:5300891 | Doi | 10.1182/blood-2010-12-325944 |
| Citation | Hampel F, et al. (2011) CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling. Blood 118(24):6321-31 |
| abstractText | B cell-specific gene ablation of Notch2 results in the loss of the marginal zone (MZ) B-cell lineage. To analyze the effects of constitutive Notch2 signaling in B cells, we have generated a transgenic mouse strain that allows the conditional expression of a constitutively active, intracellular form of Notch2 (Notch2IC). Expression of Notch2IC at the earliest developmental stages of the B-cell lineage completely abolished B-cell generation and led to the development of ectopic T cells in the bone marrow (BM), showing that Notch2IC is acting redundantly with Notch1IC in driving ectopic T-cell differentiation. In B cells clearly committed to the B-cell lineage induction of Notch2IC drove all cells toward the MZ B-cell compartment at the expense of follicular B cells. Notch2IC-expressing B cells reflected the phenotype of wild-type MZ B cells for their localization in the MZ, the expression of characteristic surface markers, their enhanced proliferation after stimulation, and increased basal activity of Akt, Erk, and Jnk. Notch2IC-driven MZ B-cell generation in the spleen was achieved even in the absence of CD19. Our results implicate that a constitutive Notch2 signal in transitional type 1 B cells is sufficient to drive MZ B-cell differentiation. |
