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

A Kallies, J Hasbold, K Fairfax, Clare Pridans, D Emslie, BS McKenzie, AM Lew, LM Corcoran, PD Hodgkin, DM Tarlinton, SL Nutt

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)555
Number of pages566
JournalImmunity
Volume26
Issue number5
Publication statusPublished - May 2007

Keywords

  • Animals
  • Antibodies/immunology
  • Antigen-Presenting Cells/cytology
  • Antigen-Presenting Cells/immunology
  • Antigen-Presenting Cells/metabolism
  • B-Cell-Specific Activator Protein/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
  • Plasma Cells/cytology
  • Plasma Cells/immunology
  • Plasma Cells/metabolism
  • Protein Binding
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism
  • Transcription Factors/deficiency
  • Transcription Factors/genetics
  • Transcription Factors/metabolism

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