title: Programming of marginal zone B-cell fate by basic Kruppel-like factor (BKLF/KLF3).
abstract: 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.
authors.affiliation: Max Planck Institute of Immunobiology, Freiburg, Germany.
authors.forename: Gleb
authors.initials: G
authors.lastname: Turchinovich
authors.forename: Thi Thanh
authors.initials: TT
authors.lastname: Vu
authors.forename: Friederike
authors.initials: F
authors.lastname: Frommer
authors.forename: Jan
authors.initials: J
authors.lastname: Kranich
authors.forename: Sonja
authors.initials: S
authors.lastname: Schmid
authors.forename: Melanie
authors.initials: M
authors.lastname: Alles
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Loubert
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Goulet
authors.forename: Ursula
authors.initials: U
authors.lastname: Zimber-Strobl
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bachl
authors.forename: Richard
authors.initials: R
authors.lastname: Pearson
authors.forename: Merlin
authors.initials: M
authors.lastname: Crossley
authors.forename: Fabien
authors.initials: F
authors.lastname: Agenès
authors.forename: Jörg
authors.initials: J
authors.lastname: Kirberg
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054503:Lymphoid Progenitor Cells / Q000378:metabolism* / Q000502:physiology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
chemical_list: D018941:Antigens, CD19; C529780:Klf3 protein, mouse; D051741:Kruppel-Like Transcription Factors