Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1.

Development of immunoglobulin-secreting plasma cells from B cells is a tightly regulated process controlled by the action of a number of transcription factors. In particular, the transcription factor Blimp-1 is a key positive regulator of plasmacytic differentiation via its ability to suppress expression of genes involved in the mature B ...
cell program. The transcription factor Ets-1 is a negative regulator of plasmacytic differentiation, as indicated by the development of increased numbers of IgM-secreting plasma cells in Ets-1 knock-out mice. We have previously shown that Ets-1-deficient B cells undergo enhanced differentiation into IgM-secreting plasma cells in response to Toll-like receptor 9 (TLR9) signaling. We now explore the mechanism by which Ets-1 limits differentiation downstream of TLR9. Our results indicate that Ets-1 physically interacts with Blimp-1, which leads to a block in Blimp-1 DNA binding activity and a reduction in the ability of Blimp-1 to repress target genes without interfering with Blimp-1 protein levels. In addition, we show that Ets-1 induces the expression of several target genes that are repressed by Blimp-1, including Pax-5. These results reveal a previously unknown mechanism for the control of Blimp-1 activity by Ets-1 and suggest that expression of Ets-1 must be down-regulated before plasmacytic differentiation can occur.
Mesh Terms:
Animals, B-Lymphocytes, COS Cells, Cell Differentiation, Cell Line, Cell Line, Tumor, Cercopithecus aethiops, Haplorhini, Humans, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Plasmacytoma, Proto-Oncogene Protein c-ets-1, Recombinant Fusion Proteins, Repressor Proteins, Spleen, Transcription Factors
J. Biol. Chem.
Date: Jan. 11, 2008
Download Curated Data For This Publication
166484
Switch View:
  • Interactions 5