title: Phorbol myristate acetate, but not CD40L, induces the differentiation of CLL B cells into Ab-secreting cells.
abstract: In this study, we investigated the capacity of chronic lymphocytic leukemia (CLL) B cells to undergo terminal differentiation into Ig-secreting plasma cells in T cell-independent and T cell-dependent responses. We used a two-step model involving stimulation with phorbol myristate acetate (PMA) and CD40L, together with cytokines (PMA/c and CD40L/c), for 7 days. We describe immunophenotypic modifications, changes in the levels of mRNA and protein for transcription factors and morphological and functional events occurring during the differentiation of CLL B cells into antibody-secreting cells (ASCs). The induction of differentiation differed significantly between the CD40L/c and PMA/c culture systems. The PMA/c culture system allowed CLL B cells to differentiate into IgM-secreting cells with an immunophenotype and molecular profile resembling those of preplasmablasts. By contrast, CD40L/c-stimulated cells had a phenotype and morphology similar to those of activated B cells and resembling those of the CLL B cells residing in the lymph node and bone marrow. These data suggest that the CLL B cells are not frozen permanently at a stage of differentiation and are able to differentiate into ASCs as appropriate stimulation are provided. The data presented here raise questions about the molecular processes and stimulation required for CLL B-cell differentiation and about the inability of CD40 ligand to induce differentiation of the CLL B cells.
authors.affiliation: EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Hussein
authors.initials: H
authors.lastname: Ghamlouch
authors.affiliation: EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Hakim
authors.initials: H
authors.lastname: Ouled-Haddou
authors.affiliation: EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Guyart
authors.affiliation: 1] EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France [2] Service d'Hématologie Clinique et Thérapie Cellulaire, CHU d'Amiens, Avenue René Laënnec, Amiens, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Regnier
authors.affiliation: 1] EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France [2] Laboratoire d'Oncobiologie Moléculaire, CHU d'Amiens, Avenue René Laënnec, Amiens, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Trudel
authors.affiliation: Service d'Hématologie Clinique et Thérapie Cellulaire, CHU d'Amiens, Avenue René Laënnec, Amiens, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Claisse
authors.affiliation: EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fuentes
authors.affiliation: 1] EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France [2] Service d'Hématologie Clinique et Thérapie Cellulaire, CHU d'Amiens, Avenue René Laënnec, Amiens, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.affiliation: 1] EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France [2] Service d'Hématologie Clinique et Thérapie Cellulaire, CHU d'Amiens, Avenue René Laënnec, Amiens, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.affiliation: 1] EA4666, Laboratoire d'Immunologie, UFR de Médecine, Université de Picardie Jules Verne, Amiens, France [2] Laboratoire d'Oncobiologie Moléculaire, CHU d'Amiens, Avenue René Laënnec, Amiens, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gubler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation / Q000276:immunology*; D000954:Antigens, Surface / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D023201:CD40 Ligand / Q000276:immunology*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D007075:Immunoglobulin M; D023201:CD40 Ligand; D013755:Tetradecanoylphorbol Acetate