Overexpression of B cell-specific activator protein (BSAP/Pax-5) in a late B cell is sufficient to suppress differentiation to an Ig high producer cell with plasma cell phenotype.
The B cell-specific activator protein (BSAP) is a DNA-binding transcription factor expressed in pro-B, pre-B, and mature B cells but not in plasma cells. We explored the role of BSAP in B cell function by creating clones in a late B cell and a plasma cell line transfected with a BSAP expression plasmid. We found that the plasma cell line MPC11, which does not produce BSAP, is still permissive to BSAP production driven by heterologous promoter. Overexpression of BSAP in a late B cell line (CH12.LX.A2) and a plasma cell line augmented cell proliferation and led to greater suppression of Ig synthesis in a late B cell line than in the plasma cell line. The reduction was seen mostly in synthesis of a secretory form of Ig. Overexpression of BSAP reduced Blimp-1 expression in CH12.LX.A2 clones but not in MPC11 clones. In addition, overexpression of BSAP in CH12.LX.A2 cells suppressed spontaneous appearance of cells with high Syndecan-1 expression and high amounts of intracytosolic as well as secreted Ig synthesis. To corroborate the above findings, we cloned nontransfected CH12.LX.A2 cells and found reduced BSAP mRNA expression in the high Ig-secreting clones, which produced more Blimp-1 mRNA with greater Syndecan-1 expression than the low Ig-secreting clones. Taken together, these results indicate that BSAP expression is sufficient to reduce Ig production in late B cells; this effect is mediated in part by suppression of differentiation to cells of plasma-cell phenotype.
Usui
T
T
Department of Clinical Bio-regulatory Science, Graduate School of Medicine, Kyoto University, Japan.
Wakatsuki
Y
Y
Matsunaga
Y
Y
Kaneko
S
S
Koseki
H
H
Kita
T
T
Kosek
H
H
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D015536:Down-Regulation / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D016130:Immunophenotyping; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D051757:PAX5 Transcription Factor; D010950:Plasma Cells / Q000145:classification / Q000166:cytology* / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D014162:Transfection
D004268:DNA-Binding Proteins; D007071:Immunoglobulin A, Secretory; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C513258:Prdm1 protein, mouse; D011509:Proteoglycans; D012333:RNA, Messenger; D012097:Repressor Proteins; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1