Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response

Nat Immunol. 2016 Mar;17(3):323-30. doi: 10.1038/ni.3348. Epub 2016 Jan 18.

Abstract

Plasma cell differentiation requires silencing of B cell transcription, while it establishes antibody-secretory function and long-term survival. The transcription factors Blimp-1 and IRF4 are essential for the generation of plasma cells; however, their function in mature plasma cells has remained elusive. We found that while IRF4 was essential for the survival of plasma cells, Blimp-1 was dispensable for this. Blimp-1-deficient plasma cells retained their transcriptional identity but lost the ability to secrete antibody. Blimp-1 regulated many components of the unfolded protein response (UPR), including XBP-1 and ATF6. The overlap in the functions of Blimp-1 and XBP-1 was restricted to that response, with Blimp-1 uniquely regulating activity of the kinase mTOR and the size of plasma cells. Thus, Blimp-1 was required for the unique physiological ability of plasma cells that enables the secretion of protective antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 6 / genetics
  • Activating Transcription Factor 6 / immunology
  • Animals
  • Cell Differentiation / immunology*
  • Cell Size
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation
  • High-Throughput Nucleotide Sequencing
  • Immunoglobulins / immunology*
  • Immunoglobulins / metabolism
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology*
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism
  • Positive Regulatory Domain I-Binding Factor 1
  • Regulatory Factor X Transcription Factors
  • Sequence Analysis, DNA
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Unfolded Protein Response / genetics
  • Unfolded Protein Response / immunology*
  • X-Box Binding Protein 1

Substances

  • Activating Transcription Factor 6
  • Atf6 protein, mouse
  • DNA-Binding Proteins
  • Immunoglobulins
  • Interferon Regulatory Factors
  • Prdm1 protein, mouse
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • Xbp1 protein, mouse
  • interferon regulatory factor-4
  • Positive Regulatory Domain I-Binding Factor 1
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse