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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.

Phorbol myristate acetate, but not CD40L, induces the differentiation of CLL B cells into Ab‐secreting cells