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Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program.

Authors
  • Shaffer, A L1
  • Lin, Kuo I
  • Kuo, Tracy C
  • Yu, Xin
  • Hurt, Elaine M
  • Rosenwald, Andreas
  • Giltnane, Jena M
  • Yang, Liming
  • Zhao, Hong
  • Calame, Kathryn
  • Staudt, Louis M
  • 1 Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Type
Published Article
Journal
Immunity
Publisher
Elsevier
Publication Date
July 2002
Volume
17
Issue
1
Pages
51–62
Identifiers
PMID: 12150891
Source
Medline
License
Unknown

Abstract

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.

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