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Phorbol myristate acetate, but not CD40L, induces the differentiation of CLL B cells into Ab‐secreting cells
Author(s) -
Ghamlouch Hussein,
OuledHaddou Hakim,
Guyart Aude,
Regnier Aline,
Trudel Stéphanie,
Claisse JeanFrançois,
Fuentes Vincent,
Royer Bruno,
Marolleau JeanPierre,
Gubler Brigitte
Publication year - 2014
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2014.37
Subject(s) - cd40 , immunophenotyping , cellular differentiation , biology , phorbol , b cell , chronic lymphocytic leukemia , bone marrow , cell culture , b 1 cell , microbiology and biotechnology , antibody , immunology , chemistry , flow cytometry , leukemia , cytotoxic t cell , protein kinase c , in vitro , signal transduction , biochemistry , genetics , gene
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.