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Prepublished online as a Blood First Edition Paper on March 27, 2003; DOI 10.1182/blood-2002-10-3161.

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Blood, 15 July 2003, Vol. 102, No. 2, pp. 592-600

IMMUNOBIOLOGY

Gene expression profiling of plasma cells and plasmablasts: toward a better understanding of the late stages of B-cell differentiation

Karin Tarte, Fenghuang Zhan, John De Vos, Bernard Klein, and John Shaughnessy, Jr

From the Institut National de la Santé et de la Recherche Médicale (INSERM) U475, Montpellier, France; Unité de Thérapie Cellulaire, Centre Hospitalier Universitaire (CHU) Montpellier, Hôpital Saint Eloi, Montpellier, France; and the Donna and Donald Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock

Plasma cells (PCs), the end point of B-cell differentiation, are a heterogeneous cell compartment comprising several cell subsets from short-lived highly proliferative plasmablasts to long-lived nondividing fully mature PCs. Whereas the major transcription factors driving the differentiation of B cells to PCs were recently identified, the subtle genetic changes that underlie the transition from plasmablasts to mature PCs are poorly understood. We recently described an in vitro model making it possible to obtain a large number of cells with the morphologic, phenotypic, and functional characteristics of normal polyclonal plasmablastic cells (PPCs). Using Affymetrix microarrays we compared the gene expression profiles of these PPCs with those of mature PCs isolated from tonsils (TPCs) and bone marrow (BMPCs), and with those of B cells purified from peripheral blood (PBB cells) and tonsils (TBCs). Unsupervised principal component analysis clearly distinguished the 5 cell populations on the basis of their differentiation and proliferation status. Detailed statistical analysis allowed the identification of 85 PC genes and 40 B-cell genes, overexpressed, respectively, in the 3 PC subsets or in the 2 B-cell subsets. In addition, several signaling molecules and antiapoptotic proteins were found to be induced in BMPCs compared with PPCs and could be involved in the accumulation and prolonged survival of BMPCs in close contact with specialized stromal microenvironment. These data should help to better understand the molecular events that regulate commitment to a PC fate, mediate PC maintenance in survival niches, and could facilitate PC immortalization in plasma cell dyscrasias.


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