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CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling

Item Type:Article
Title:CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling
Creators Name:Hampel, F., Ehrenberg, S., Hojer, C., Draeseke, A., Marschall-Schröter, G., Kühn, R., Mack, B., Gires, O., Vahl, C.J., Schmidt-Supprian, M., Strobl, L.J. and Zimber-Strobl, U.
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.
Keywords:B-Lymphocytes, Bone Marrow Cells, CD19 Antigens, Cell Lineage, Cell Proliferation, Cultured Cells, Genetic Crosses, Heterozygote, Homozygote, Lymphopoiesis, MAP Kinase Signaling System, Notch2 Receptor, Phosphorylation, Post-Translational Protein Processing, Spleen, T-Lymphocytes, Animals, Mice, Knockout Mice, Transgenic Mice
Publisher:American Society of Hematology
Page Range:6321-631
Date:8 December 2011
Official Publication:https://doi.org/10.1182/blood-2010-12-325944
PubMed:View item in PubMed

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