Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program.
Blimp-1, a transcriptional repressor, drives the terminal differentiation of B cells to plasma cells. Using DNA microarrays, we found that introduction of Blimp-1 into B cells blocked expression of a remarkably large set of genes, while a much smaller number was induced. Blimp-1 initiated this cascade of gene expression changes by directly repressing genes encoding several transcription factors, including Spi-B and Id3, that regulate signaling by the B cell receptor. Blimp-1 also inhibited immunoglobulin class switching by blocking expression of AID, Ku70, Ku86, DNA-PKcs, and STAT6. These findings suggest that Blimp-1 promotes plasmacytic differentiation by extinguishing gene expression important for B cell receptor signaling, germinal center B cell function, and proliferation while allowing expression of important plasma cell genes such as XBP-1.
Shaffer
A L
AL
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Lin
Kuo I
KI
Kuo
Tracy C
TC
Yu
Xin
X
Hurt
Elaine M
EM
Rosenwald
Andreas
A
Giltnane
Jena M
JM
Yang
Liming
L
Zhao
Hong
H
Calame
Kathryn
K
Staudt
Louis M
LM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D017578:Immunoglobulin Class Switching; D051379:Mice; D018448:Models, Immunological; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C513258:Prdm1 protein, mouse; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1