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 RIS Download
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