Blimp-1-dependent repression of Pax-5 is required for differentiation of B cells to immunoglobulin M-secreting plasma cells

Mol Cell Biol. 2002 Jul;22(13):4771-80. doi: 10.1128/MCB.22.13.4771-4780.2002.

Abstract

B-cell lineage-specific activator protein (BSAP), encoded by the Pax-5 gene, is critical for B-cell lineage commitment and B-cell development but is not expressed in terminally differentiated B cells. We demonstrate a direct connection between BSAP and B-lymphocyte-induced maturation protein 1 (Blimp-1), a transcriptional repressor that is sufficient to drive plasmacytic differentiation. Blimp-1 binds a site on the Pax-5 promoter in vitro and in vivo and represses the Pax-5 promoter in a binding-site-dependent manner. By ectopically expressing Blimp-1 or a competitive inhibitor of Blimp-1, we show that Blimp-1 is both necessary and sufficient to repress Pax-5 during plasmacytic differentiation of primary splenic B cells. Blimp-1-dependent repression of Pax-5 is sufficient to regulate BSAP targets CD19 and J chain and is necessary but not sufficient to induce XBP-1. We further show that repression of Pax-5 is required for Blimp-1 to drive differentiation of splenocytes to immunoglobulin M-secreting cells. Thus, repression of Pax-5 plays a critical role in the Blimp-1-dependent program of plasmacytic differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Binding Sites
  • Cell Differentiation*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Immunoglobulin J-Chains / metabolism
  • Immunoglobulin M / metabolism*
  • Mice
  • PAX5 Transcription Factor
  • Positive Regulatory Domain I-Binding Factor 1
  • Promoter Regions, Genetic
  • Regulatory Factor X Transcription Factors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • X-Box Binding Protein 1

Substances

  • Antigens, CD19
  • DNA-Binding Proteins
  • Immunoglobulin J-Chains
  • Immunoglobulin M
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Prdm1 protein, mouse
  • Regulatory Factor X Transcription Factors
  • Repressor Proteins
  • Transcription Factors
  • X-Box Binding Protein 1
  • Xbp1 protein, mouse
  • Positive Regulatory Domain I-Binding Factor 1