IL-21 induces the apoptosis of resting and activated primary B cells.
Cytokines play an important role in regulating the development and homeostasis of B cells by controlling their viability. In this study, we show that the recently described T cell-derived cytokine IL-21 induces the apoptosis of resting primary murine B cells. In addition, the activation of primary B cells with IL-4, LPS, or anti-CD40 Ab does not prevent IL-21-mediated apoptosis. The induction of apoptosis by IL-21 correlates with a down-regulation in the expression of Bcl-2 and Bcl-x(L), two antiapoptotic members of the Bcl-2 family. Furthermore, the reconstitution of Bcl-x(L) or Bcl-2 expression protects primary B cells from IL-21-induced apoptosis. In addition, a short-term preactivation of B cells with anti-CD40 Ab confers protection from IL-21-mediated apoptosis through the up-regulation of Bcl-x(L). These studies reveal a novel pathway that mediates B cell apoptosis via the IL-21R and suggest that IL-21 may play a role in regulating B cell homeostasis.
Mehta
Devangi S
DS
Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Genetics Institute, Wyeth Research, Cambridge, MA 02140, USA.
Wurster
Andrea L
AL
Whitters
Matthew J
MJ
Young
Deborah A
DA
Collins
Mary
M
Grusby
Michael J
MJ
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D006131:Growth Inhibitors / Q000502:physiology; D007106:Immune Sera / Q000502:physiology; D007075:Immunoglobulin M / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000502:physiology*; D007399:Interphase / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology; D051020:bcl-X Protein; D000098546:Interleukin-21
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; C494812:Bcl2l1 protein, mouse; D019013:CD40 Antigens; D006131:Growth Inhibitors; D007106:Immune Sera; D007075:Immunoglobulin M; D007378:Interleukins; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C044203:anti-IgM; D051020:bcl-X Protein; D015847:Interleukin-4; D000098546:Interleukin-21