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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

Authors
 Katsutoshi Ozaki  ;  Rosanne Spolski  ;  Warren J. Leonard  ;  Peter E. Lipsky  ;  Herbert C. Morse  ;  Derry C. Roopenian  ;  Shreeram Akilesh  ;  Daniel J. Shaffer  ;  Patrick Hwu  ;  Chen-Feng Qi  ;  Gang Wang  ;  Hyoung-Pyo Kim  ;  Rachel Ettinger 
Citation
 JOURNAL OF IMMUNOLOGY, Vol.173(9) : 5361-5371, 2004 
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
 0022-1767 
Issue Date
2004
MeSH
Animals ; Apoptosis/genetics ; Apoptosis/immunology ; B-Lymphocyte Subsets/cytology* ; B-Lymphocyte Subsets/immunology* ; B-Lymphocyte Subsets/metabolism ; CellDivision/genetics ; CellDivision/immunology ; CellSeparation ; Cells, Cultured ; DNA-Binding Proteins/antagonists & inhibitors ; DNA-Binding Proteins/biosynthesis* ; Humans ; Immunoglobulin Class Switching/genetics ; Interleukins/biosynthesis ; Interleukins/genetics ; Interleukins/physiology* ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Lymphocyte Count ; Membrane Glycoproteins/biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Mutant Strains ; Mice, Transgenic ; PAX5 Transcription Factor ; PlasmaCells/cytology* ; PlasmaCells/immunology* ; PlasmaCells/metabolism ; Positive Regulatory Domain I-Binding Factor 1 ; Proteoglycans/biosynthesis ; Proto-Oncogene Proteins/biosynthesis* ; Proto-Oncogene Proteins c-bcl-6 ; Repressor Proteins/biosynthesis* ; Spleen/anatomy & histology ; Spleen/cytology ; Spleen/immunology ; Syndecans ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/biosynthesis* ; Up-Regulation/immunology
Abstract
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.
Files in This Item:
T200404375.pdf Download
DOI
10.4049/jimmunol.173.9.5361
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/112946
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