title: Forced KLF4 expression increases the generation of mature plasma cells and uncovers a network linked with plasma cell stage.
abstract: A role of the transcription factor Krüppel-like factor 4 (KLF4) in the generation of mature plasma cells (PC) is unknown. Indeed, KLF4 is critical in controlling the differentiation of various cell linages, particularly monocytes and epithelial cells. KLF4 is expressed at low levels in pro-B cells and its expression increases as they mature into pre-B cells, resting naïve B cells and memory B cells. We show here that KLF4 is expressed in human bone marrow plasma cells and its function was studied using an in vitro model of differentiation of memory B cells into long lived plasma cells. KLF4 is rapidly lost when memory B cells differentiate into highly cell cycling plasmablasts, poorly cycling early plasma cells and then quiescent long-lived plasma cells. A forced expression of KLF4 in plasmablasts enhances the yield of their differentiation into early plasma cell and long lived plasma cells, by inhibiting apoptosis and upregulating previously unknown plasma cell pathways.
authors.affiliation: a Department of Biological Hematology , CHU Montpellier , Montpellier , France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Schoenhals
authors.affiliation: b Institute of Human Genetics, CNRS-UPR1142 , Montpellier , France.
authors.forename: Michel
authors.initials: M
authors.lastname: Jourdan
authors.affiliation: c Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg , Heidelberg , Germany.|d Nationales Centrum für Tumorerkrankungen , Heidelberg , Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Seckinger
authors.affiliation: e INSERM, U1040 , Montpellier , France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Pantesco
authors.affiliation: c Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg , Heidelberg , Germany.|d Nationales Centrum für Tumorerkrankungen , Heidelberg , Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.affiliation: b Institute of Human Genetics, CNRS-UPR1142 , Montpellier , France.
authors.forename: Alboukadel
authors.initials: A
authors.lastname: Kassambara
authors.affiliation: a Department of Biological Hematology , CHU Montpellier , Montpellier , France.|b Institute of Human Genetics, CNRS-UPR1142 , Montpellier , France.|f University of Montpellier 1, UFR de Médecine , Montpellier , France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.affiliation: a Department of Biological Hematology , CHU Montpellier , Montpellier , France.|b Institute of Human Genetics, CNRS-UPR1142 , Montpellier , France.|f University of Montpellier 1, UFR de Médecine , Montpellier , France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D020869:Gene Expression Profiling; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D020169:Caspases
keywords: B cell; KLF4; Plasma cell; differentiation; maturation