1. Forced KLF4 expression increases the generation of mature plasma cells and uncovers a network linked with plasma cell stage
- Author
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Anja Seckinger, Alboukadel Kassambara, Matthieu Schoenhals, Jérôme Moreaux, Véronique Pantesco, Bernard Klein, Michel Jourdan, Dirk Hose, Department of Biological Hematology , CHU Montpellier , Montpellier, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg , Heidelberg,and 4d Nationales Centrum für Tumorerkrankungen , Heidelberg, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1), Hematology, and Basic (bio-) Medical Sciences
- Subjects
0301 basic medicine ,Cellular differentiation ,[SDV]Life Sciences [q-bio] ,Naive B cell ,Cell ,Plasma Cells ,Kruppel-Like Transcription Factors ,Bone Marrow Cells/cytology ,Bone Marrow Cells ,Plasma cell ,Biology ,Cell Line ,03 medical and health sciences ,Kruppel-Like Factor 4 ,Cell Cycle News & Views ,stomatognathic system ,Report ,medicine ,Humans ,Genetics(clinical) ,Molecular Biology ,B cell ,ComputingMilieux_MISCELLANEOUS ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,CD40 ,hematology ,Caspases/metabolism ,Gene Expression Profiling ,Cell Differentiation ,Cell Biology ,Cell biology ,Plasma Cells/cytology ,030104 developmental biology ,medicine.anatomical_structure ,KLF4 ,Apoptosis ,Caspases ,Immunology ,biology.protein ,Developmental Biology ,Kruppel-Like Transcription Factors/metabolism - Abstract
A role of the transcription factor Kruppel-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 naive 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.
- Published
- 2016