title: CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling.
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.
authors.affiliation: Department of Gene Vectors, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, Munich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Hampel
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ehrenberg
authors.forename: Caroline
authors.initials: C
authors.lastname: Hojer
authors.forename: Anne
authors.initials: A
authors.lastname: Draeseke
authors.forename: Gabriele
authors.initials: G
authors.lastname: Marschall-Schröter
authors.forename: Ralf
authors.initials: R
authors.lastname: Kühn
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mack
authors.forename: Olivier
authors.initials: O
authors.lastname: Gires
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Vahl
authors.forename: Marc
authors.initials: M
authors.lastname: Schmidt-Supprian
authors.forename: Lothar J
authors.initials: LJ
authors.lastname: Strobl
authors.forename: Ursula
authors.initials: U
authors.lastname: Zimber-Strobl
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D003433:Crosses, Genetic; D006579:Heterozygote; D006720:Homozygote; D038041:Lymphopoiesis; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; C497765:Notch2 protein, mouse; D051883:Receptor, Notch2