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Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6.

IL-21 is a type I cytokine whose receptor is expressed on T, B, and NK cells. Within the B cell lineage, IL-21 regulates IgG1 production and cooperates with IL-4 for the production of multiple Ab classes in vivo. Using IL-21-transgenic mice and hydrodynamics-based gene delivery of IL-21 plasmid DNA into wild-type mice as well as in vitro studies, we demonstrate that although IL-21 induces death of resting B cells, it promotes differentiation of B cells into postswitch and plasma cells. Thus, IL-21 differentially influences B cell fate depending on the signaling context, explaining how IL-21 can be proapoptotic for B cells in vitro yet critical for Ag-specific Ig production in vivo. Moreover, we demonstrate that IL-21 unexpectedly induces expression of both Blimp-1 and Bcl-6, indicating mechanisms as to how IL-21 can serve as a complex regulator of B cell maturation and terminal differentiation. Finally, BXSB-Yaa mice, which develop a systemic lupus erythematosus-like disease, have greatly elevated IL-21, suggesting a role for IL-21 in the development of autoimmune disease.

Pubmed ID: 15494482


  • Ozaki K
  • Spolski R
  • Ettinger R
  • Kim HP
  • Wang G
  • Qi CF
  • Hwu P
  • Shaffer DJ
  • Akilesh S
  • Roopenian DC
  • Morse HC
  • Lipsky PE
  • Leonard WJ


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

November 1, 2004

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK56597

Mesh Terms

  • Animals
  • Apoptosis
  • B-Cell-Specific Activator Protein
  • B-Lymphocyte Subsets
  • Cell Division
  • Cell Separation
  • Cells, Cultured
  • DNA-Binding Proteins
  • Humans
  • Immunoglobulin Class Switching
  • Interleukins
  • Lupus Erythematosus, Systemic
  • Lymphocyte Count
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Plasma Cells
  • Proteoglycans
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Repressor Proteins
  • Spleen
  • Syndecans
  • Transcription Factors
  • Up-Regulation