Plenary paper Generation of polyclonal plasmablasts from peripheral blood B cells: a normal counterpart of malignant plasmablasts

A new way to identify tumor-specific genes is to compare gene expression profiles between malignant cells and their autologous normal counterparts. In pa-tients with multiple myeloma, a major plasma cell disorder, normal plasma cells are not easily attainable in vivo. We report here that in vitro differentiation of periph-eral blood B lymphocytes, purified from healthy donors and from patients with multiple myeloma, makes it possible to obtain a homogeneous population of nor-mal plasmablastic cells. These cells were identified by their morphology, pheno-type, production of polyclonal immuno-globulins, and expression of major tran-scription factors involved in B-cell differentiation. Oligonucleotide microar-ray analysis shows that these polyclonal plasmablastic cells have a gene expres-sion pattern close to that of normal bone marrow–derived plasma cells. Detailed analysis of genes statistically differen-tially expressed between normal and tu-mor plasma cells allows the identification of myeloma-specific genes, including on-cogenes and genes coding for tumor anti-gens. These data should help to disclose the molecular mechanisms of myeloma pathogenesis and to define new therapeu-tic targets in this still fatal malignancy. In addition, the comparison of gene expres-sion between plasmablastic cells and B cells provides a new and powerful tool to identify genes specifically involved in nor-mal plasma cell differentiation. (Blood