Cutting edge: cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein protects germinal center B cells from apoptosis during germinal center reactions.
During germinal center (GC) reactions, follicular dendritic cells are believed to select memory B lymphocytes by switching off apoptosis in the successfully binding B cells. The cellular signals involved in this process are largely unknown. Here, we show that GC B lymphocytes have a long isoform of the cellular homologue of the viral Fas-associated death domain-like IL-1-converting enzyme-like inhibitory protein (cFLIP(L)), which is capable of inhibiting death receptor-induced caspase activation. In isolated GC B cells, cFLIP(L) decays rapidly even without Fas ligation, and this results in activation of caspase activity and apoptosis. Contact with follicular dendritic cells prevents cFLIP(L) degradation and blocks all signs of apoptosis, even in the presence of anti-Fas ABS: cFLIP(L) expression is sustained by CD40 ligation as well, suggesting that at least at some stage of the GC reaction activated T cells may help selected B cells to leave the follicular dendritic cell network without becoming apoptotic.
van Eijk
M
M
Department of Cell Biology and Histology, Cellular Immunology Group, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
Medema
J P
JP
de Groot
C
C
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D061945:Caspase Inhibitors; D002450:Cell Communication / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D053200:Fas-Associated Death Domain Protein; D018858:Germinal Center / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D015843:Serpins / Q000378:metabolism / Q000502:physiology*; D014764:Viral Proteins; D019014:fas Receptor / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D061945:Caspase Inhibitors; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D020033:Protein Isoforms; D015843:Serpins; D014764:Viral Proteins; D019014:fas Receptor; D023201:CD40 Ligand; C074641:interleukin-1beta-converting enzyme inhibitor