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 patients 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 peripheral blood B lymphocytes, purified from healthy donors and from patients with multiple myeloma, makes it possible to obtain a homogeneous population of normal plasmablastic cells. These cells were identified by their morphology, phenotype, production of polyclonal immunoglobulins, and expression of major transcription factors involved in B-cell differentiation. Oligonucleotide microarray analysis shows that these polyclonal plasmablastic cells have a gene expression pattern close to that of normal bone marrow-derived plasma cells. Detailed analysis of genes statistically differentially expressed between normal and tumor plasma cells allows the identification of myeloma-specific genes, including oncogenes and genes coding for tumor antigens. These data should help to disclose the molecular mechanisms of myeloma pathogenesis and to define new therapeutic targets in this still fatal malignancy. In addition, the comparison of gene expression between plasmablastic cells and B cells provides a new and powerful tool to identify genes specifically involved in normal plasma cell differentiation.
Tarte
Karin
K
Unite de Thérapie Cellulaire, CHU Montpellier, France.
De Vos
John
J
Thykjaer
Thomas
T
Zhan
Fenghuang
F
Fiol
Geneviève
G
Costes
Valérie
V
Rème
Thierry
T
Legouffe
Eric
E
Rossi
Jean-François
JF
Shaughnessy
John
J
Ørntoft
Torben F
TF
Klein
Bernard
B
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D018941:Antigens, CD19 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000951:Antigens, Neoplasm; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics; D009244:NAD+ Nucleosidase / Q000032:analysis; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
D015703:Antigens, CD; D018941:Antigens, CD19; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D007136:Immunoglobulins; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; C072012:MAGEB2 protein, human; C489518:Mageb1 protein, mouse; C512965:Mageb2 protein, mouse; C489519:Mageb3 protein, mouse; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C093962:synovial sarcoma X breakpoint proteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1