Germinal center B cell apoptosis requires both caspase and cathepsin activity.
Follicular dendritic cells (FDCs) select B cells during germinal center (GC) reactions. The B cells that are able to bind to the FDCs receive a signal that leads to the termination of endonuclease activity in the nuclei of those B cells. This signal must be in addition to the signals transferred through the cross-linkage of the B cell receptors and signals resulting from the interactions of the adhesion molecules lymphocyte function-associated Ag-1 and very late Ag-4 with ICAM-1 and VCAM-1, respectively. In this report, we present evidence that the FDCs silence all apoptotic processes in GC B lymphocytes and additionally switch off pre-present endonuclease activity. We also show that GC B cell apoptosis requires cathepsin activity downstream of caspase-3. This cathepsin activity is directly connected to endonuclease activity and therefore may be an interesting target for the antiapoptotic factors produced by FDCs.
van Eijk
M
M
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands.
de Groot
C
C
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D004720:Endonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D018858:Germinal Center / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D014066:Palatine Tonsil; D015398:Signal Transduction / Q000276:immunology
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D004720:Endonucleases; D002403:Cathepsins; D020169:Caspases; D007930:Leucine; C108192:aloxistatin