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Programming of marginal zone B-cell fate by basic Krüppel-like factor (BKLF/KLF3).
Blood 117, 3780-3792 (2011)
Splenic marginal zone (MZ) B cells are a lineage distinct from follicular and peritoneal B1 B cells. They are located next to the marginal sinus where blood is released. Here they pick up antigens and shuttle the load onto follicular dendritic cells inside the follicle. On activation, MZ B cells rapidly differentiate into plasmablasts secreting antibodies, thereby mediating humoral immune responses against blood-borne type 2 T-independent antigens. As Krüppel-like factors are implicated in cell differentiation/function in various tissues, we studied the function of basic Krüppel-like factor (BKLF/KLF3) in B cells. Whereas B-cell development in the bone marrow of KLF3-transgenic mice was unaffected, MZ B-cell numbers in spleen were increased considerably. As revealed in chimeric mice, this occurred cell autonomously, increasing both MZ and peritoneal B1 B-cell subsets. Comparing KLF3-transgenic and nontransgenic follicular B cells by RNA-microarray revealed that KLF3 regulates a subset of genes that was similarly up-regulated/down-regulated on normal MZ B-cell differentiation. Indeed, KLF3 expression overcame the lack of MZ B cells caused by different genetic alterations, such as CD19-deficiency or blockade of B-cell activating factor-receptor signaling, indicating that KLF3 may complement alternative nuclear factor-κB signaling. Thus, KLF3 is a driving force toward MZ B-cell maturation.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
t-cells; in-vivo; pre-b; lymphocyte-activation; receptor signals; co-repressor; baff; transcription; expression; survival
Language
english
Publication Year
2011
HGF-reported in Year
2011
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Journal
Blood
Quellenangaben
Volume: 117,
Issue: 14,
Pages: 3780-3792
Publisher
American Society of Hematology
Publishing Place
Washington, USA
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Immune Response and Infection
PSP Element(s)
G-501500-003
PubMed ID
21297003
Scopus ID
79953833433
Erfassungsdatum
2011-09-08