Initiation of plasma-cell differentiation is independent of the transcription factor Blimp-1

Immunity. 2007 May;26(5):555-66. doi: 10.1016/j.immuni.2007.04.007.


Blimp-1 is considered an essential regulator of the terminal differentiation of B cells into antibody-secreting plasma cells. We show here that Rag1-/- mice reconstituted with fetal liver cells homozygous for a DNA-binding-deficient mutant of Prdm1 (the gene encoding Blimp-1) lack a defined plasma-cell compartment, yet show detectable amounts of all immunoglobulin isotypes. In vitro analysis revealed that Blimp-1 is not required for the initiation of antibody secretion but is essential for subsequent high immunoglobulin production. Blimp-1-independent differentiation was blocked at a preplasmablast stage characterized by decreased Pax5 expression and the activation of plasma-cell genes. Analysis of Blimp-1-sufficient differentiation revealed a phase prior to Blimp-1 expression in which several genes normally repressed by Pax5 are re-expressed, suggesting that plasma-cell differentiation is initiated by the inhibition of Pax5 function. Our results indicate that full plasma-cell differentiation but not commitment to the plasma-cell fate requires the expression of functional Blimp-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • B-Lymphocytes / metabolism
  • Cell Differentiation* / immunology
  • Cells, Cultured
  • DNA / metabolism
  • Gene Expression Regulation
  • Immunoglobulin G / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • PAX5 Transcription Factor / metabolism
  • Plasma Cells / cytology*
  • Plasma Cells / immunology
  • Plasma Cells / metabolism*
  • Positive Regulatory Domain I-Binding Factor 1
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Antibodies
  • Immunoglobulin G
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Prdm1 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • DNA
  • Positive Regulatory Domain I-Binding Factor 1