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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. ; Zimber-Strobl, U.

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

Blood 118, 6321-6331 (2011)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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 allowing 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, 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 towards 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 with respect to 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 T1 B cells is sufficient to drive MZ B cell differentiation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords no keywords
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 118, Issue: 14, Pages: 6321-6331 Article Number: , Supplement: ,
Publisher American Society of Hematology
Publishing Place Washington, DC, USA
Reviewing status Peer reviewed