Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation

Nat Immunol. 2016 Mar;17(3):331-43. doi: 10.1038/ni.3349. Epub 2016 Jan 18.


The transcription factor Blimp-1 is necessary for the generation of plasma cells. Here we studied its functions in plasmablast differentiation by identifying regulated Blimp-1 target genes. Blimp-1 promoted the migration and adhesion of plasmablasts. It directly repressed genes encoding several transcription factors and Aicda (which encodes the cytidine deaminase AID) and thus silenced B cell-specific gene expression, antigen presentation and class-switch recombination in plasmablasts. It directly activated genes, which led to increased expression of the plasma cell regulator IRF4 and proteins involved in immunoglobulin secretion. Blimp-1 induced the transcription of immunoglobulin genes by controlling the 3' enhancers of the loci encoding the immunoglobulin heavy chain (Igh) and κ-light chain (Igk) and, furthermore, regulated the post-transcriptional expression switch from the membrane-bound form of the immunoglobulin heavy chain to its secreted form by activating Ell2 (which encodes the transcription-elongation factor ELL2). Notably, Blimp-1 recruited chromatin-remodeling and histone-modifying complexes to regulate its target genes. Hence, many essential functions of plasma cells are under the control of Blimp-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Migration Assays, Leukocyte
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Chromatin Immunoprecipitation
  • Electrophoretic Mobility Shift Assay
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Regulation
  • HEK293 Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology*
  • Immunoglobulin kappa-Chains / genetics
  • Immunoglobulin kappa-Chains / immunology*
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology*
  • Mass Spectrometry
  • Mice
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism
  • Positive Regulatory Domain I-Binding Factor 1
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA
  • Transcription Factors / genetics
  • Transcription Factors / immunology*


  • Immunoglobulin Heavy Chains
  • Immunoglobulin kappa-Chains
  • Interferon Regulatory Factors
  • Prdm1 protein, mouse
  • Transcription Factors
  • interferon regulatory factor-4
  • Positive Regulatory Domain I-Binding Factor 1