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Plasmacytic transcription factor Blimp-1 is repressed by Bach2 in B cells.

Bach2 is a B cell-specific transcription repressor whose deficiency in mice causes a reduced class switch recombination and a reduced somatic hypermutation of immunoglobulin genes. Little is known about the direct target genes of Bach2 in B cells. By analyzing various B cell and plasma cell lines, we showed that the expression patterns of Bach2 and Blimp-1 (B lymphocyte-induced maturation protein 1), a master regulator of plasma cell differentiation, are mutually exclusive. The reporter gene of the Blimp-1 gene (Prdm1) was repressed by the overexpression of Bach2 in B cell lines. The heterodimer of Bach2/MafK bound to the Maf recognition element located upstream of the Prdm1 promoter in an electrophoretic mobility shift assay. The binding of MafK in B cells to the Prdm1 Maf recognition element was confirmed by chromatin immunoprecipitation assays. When MafK was purified from the BAL17 B cell line, a significant portion of it was present as a heterodimer with Bach2, with no apparent formation of MafK homodimer. These results strongly suggest that Bach2 represses the expression of Blimp-1 together with MafK in B cells prior to plasma cell differentiation. Accordingly, the knockdown of Bach2 mRNA using short hairpin RNA in BAL17 cells resulted in higher levels of Prdm1 expression after the stimulation of B cell receptor by surface IgM cross-linking. Induction of Prdm1 was more robust and faster in primary Bach2-deficient B cells than in wild-type control B cells upon lipopolysaccharide stimulation. Therefore, the Prdm1 regulation in B cells involves the repression by Bach2, which may be cancelled upon terminal plasma cell differentiation.

Pubmed ID: 17046816

Authors

  • Ochiai K
  • Katoh Y
  • Ikura T
  • Hoshikawa Y
  • Noda T
  • Karasuyama H
  • Tashiro S
  • Muto A
  • Igarashi K

Journal

The Journal of biological chemistry

Publication Data

December 15, 2006

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes
  • Base Sequence
  • Basic-Leucine Zipper Transcription Factors
  • Cell Line
  • Chromatin Immunoprecipitation
  • DNA Primers
  • Dimerization
  • Mice
  • Molecular Sequence Data
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors