Expression of transcription factors Pu.1, Spi-B, Blimp-1, BSAP and oct-2 in normal human plasma cells and in multiple myeloma cells.
Differentiation of B lymphocytes into plasma cells is regulated by the interaction of distinct transcription factors (TFs) which activate gene expression in a lineage- and stage-specific pattern. Using reverse transcription polymerase chain reaction, we studied the expression of five TFs (octamer binding factor oct-2, ets family members PU.1 and Spi-B, pax gene family member BSAP, and Blimp-1) in (1) human cell lines with a plasma cell phenotype, (2) primary malignant plasma cells [obtained from patients with plasma cell leukaemia (PCL) and multiple myeloma], and (3) normal human plasma cells generated in vitro or isolated from normal bone marrows. The expression pattern was compared with TFs expressed by normal CD19+ B lymphocytes and by B cells from chronic lymphocytic leukaemia patients. Our results showed that plasma cells expressed a restricted set of TFs compared with CD19+ B lymphocytes, with continued expression of Spi-B and oct-2, increased Blimp-1 expression, and downregulation of BSAP and PU.1. Cells from PCL lost Spi-B and PU.1 expression completely and expressed only oct-2 and Blimp-1, and thus resembled plasma cell lines. Human plasma cell differentiation therefore seems to be positively regulated by Blimp-1; whether this TF has any oncogenic potential will have to be analysed in future studies.
Nagy
Monika
M
Division of Hematology, University Hospital Geneva, Geneva, Switzerland.
Chapuis
Bernard
B
Matthes
Thomas
T
D018941:Antigens, CD19; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism*; D050813:Octamer Transcription Factor-2; D051757:PAX5 Transcription Factor; D010950:Plasma Cells / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D018941:Antigens, CD19; D004268:DNA-Binding Proteins; D050813:Octamer Transcription Factor-2; D051757:PAX5 Transcription Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C497281:PAX5 protein, human; C058435:POU2F2 protein, human; C087042:PRDM1 protein, human; C076877:SPIB protein, human