1. CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling.
- Author
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Hampel F, Ehrenberg S, Hojer C, Draeseke A, Marschall-Schröter G, Kühn R, Mack B, Gires O, Vahl CJ, Schmidt-Supprian M, Strobl LJ, and Zimber-Strobl U
- Subjects
- Animals, Antigens, CD19 genetics, B-Lymphocytes metabolism, Bone Marrow Cells metabolism, Cell Lineage, Cell Proliferation, Cells, Cultured, Crosses, Genetic, Heterozygote, Homozygote, Mice, Mice, Knockout, Mice, Transgenic, Phosphorylation, Protein Processing, Post-Translational, Receptor, Notch2 genetics, Spleen metabolism, T-Lymphocytes cytology, T-Lymphocytes metabolism, Antigens, CD19 metabolism, B-Lymphocytes cytology, Lymphopoiesis, MAP Kinase Signaling System, Receptor, Notch2 metabolism, Spleen cytology
- Abstract
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.
- Published
- 2011
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