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CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling.
Blood 118, 6321-6331 (2011)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
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10.558
2.337
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59
Anmerkungen
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
no keywords
Sprache
englisch
Veröffentlichungsjahr
2011
HGF-Berichtsjahr
2011
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Zeitschrift
Blood
Quellenangaben
Band: 118,
Heft: 14,
Seiten: 6321-6331
Verlag
American Society of Hematology
Verlagsort
Washington, DC, USA
Begutachtungsstatus
Peer reviewed
Institut(e)
Research Unit Gene Vector (AGV)
Institute of Developmental Genetics (IDG)
CCG Molecular Oncology (AGV-KON)
Institute of Developmental Genetics (IDG)
CCG Molecular Oncology (AGV-KON)
POF Topic(s)
30203 - Molecular Targets and Therapies
30204 - Cell Programming and Repair
30204 - Cell Programming and Repair
Forschungsfeld(er)
Immune Response and Infection
Genetics and Epidemiology
Genetics and Epidemiology
PSP-Element(e)
G-501500-003
G-500500-001
G-520700-001
G-500500-001
G-520700-001
PubMed ID
21795747
Scopus ID
83455196170
Erfassungsdatum
2011-11-08