CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling
| Autor: | Ralf Kühn, Marc Schmidt-Supprian, Lothar J. Strobl, Franziska Hampel, Gabriele Marschall-Schröter, Stefanie Ehrenberg, Caroline Hojer, Anne Draeseke, Brigitte Mack, Christoph J. Vahl, Ursula Zimber-Strobl, Olivier Gires |
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| Rok vydání: | 2011 |
| Předmět: |
Heterozygote
MAP Kinase Signaling System T-Lymphocytes Antigens CD19 Immunology Bone Marrow Cells Mice Transgenic Biochemistry CD19 Mice Marginal zone B-cell medicine Animals Cell Lineage Receptor Notch2 Lymphopoiesis Phosphorylation Protein kinase B Cells Cultured Crosses Genetic Cell Proliferation Mice Knockout B-Lymphocytes biology Cell growth Homozygote Cell Biology Hematology Marginal zone Cell biology medicine.anatomical_structure biology.protein Bone marrow Signal transduction Protein Processing Post-Translational Spleen |
| Zdroj: | Blood. 118:6321-6331 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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