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

Submitted October 18, 2002
Accepted March 11, 2003
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
Unite de Therapie Cellulaire, CHU Montpellier, Montpellier, France
Unite 475, INSERM, Montpellier, France
Donna and Donald Lambert Laboratory of Myeloma Genetics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
* Corresponding author; email: klein{at}montp.inserm.fr.
Plasma cells (PC), 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 non-dividing fully mature PC. Whereas the major transcription factors driving the differentiation of B cells to PC were recently identified, the subtle genetic changes that underlie the transition from plasmablasts to mature PC 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 (PPC). Using Affymetrix microarrays we compared here the gene expression profile of these PPC with those of mature PC isolated from tonsils (TPC) and bone marrow (BMPC), and with those of B cells purified from peripheral blood (PBB) and tonsils (TBC). Unsupervised principal component analysis clearly distinguished the five 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 three PC subsets or in the two B-cell subsets. In addition, several signaling molecules, and anti-apoptotic proteins were found to be induced in BMPC compared to PPC and could be involved in the accumulation and prolonged survival of BMPC 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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