Germinal center B cell apoptosis requires both caspase and cathepsin activity

J Immunol. 1999 Sep 1;163(5):2478-82.

Abstract

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.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis / immunology*
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / immunology
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / metabolism*
  • Cells, Cultured
  • Cysteine Proteinase Inhibitors / pharmacology
  • Dendritic Cells / immunology
  • Endonucleases / antagonists & inhibitors
  • Endonucleases / metabolism
  • Enzyme Activation / immunology
  • Germinal Center / cytology*
  • Germinal Center / enzymology*
  • Germinal Center / immunology
  • Humans
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Palatine Tonsil
  • Signal Transduction / immunology

Substances

  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Endonucleases
  • Cathepsins
  • Caspases
  • Leucine
  • aloxistatin