Signaling through HLA-DR induces PKC beta-dependent B cell death outside rafts.
Signals through HLA-DR molecules contribute to optimal activation of antigen-presenting cells (APC) during T cell/APC interactions participating in the generation of productive interactions, and to the induction of APC death, which has been postulated to play a role in the termination of the immune response. To understand how these molecules accommodate both cellular responses, we studied the not yet well-defined signaling events and the biochemical requirements for HLA-DR-mediated death. We demonstrate that in B cells the HLA-DR-activated protein kinase C (PKC) beta is required for HLA-DR-mediated death whereas the HLA-DR-activated Src family of PTK is redundant. In contrast to HLA-DR-mediated activation of Src kinase Lyn, the aggregation of HLA-DR molecules in lipid rafts is not required for HLA-DR-mediated PKC beta activation nor for the induction of cell death. Indeed, the bulk of HLA-DR-activated PKC beta reside outside rafts. This is the first report showing that HLA-DR-induced PKC beta activation is essential for the induction of B cell death via HLA-DR, and that these HLA-DR-mediated events do not require the integrity of rafts.
Guo
Wenyan
W
Centre de Recherche en Rhumatologie et Immunologie, CHUL, Université Laval, Québec, Canada.
Castaigne
Jean-Gabriel
JG
Mooney
Nuala
N
Charron
Dominique
D
Al-Daccak
Reem
R
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D016923:Cell Death; D002460:Cell Line; D006684:HLA-DR Antigens / Q000502:physiology*; D021962:Membrane Microdomains / Q000201:enzymology / Q000276:immunology*; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D021381:Protein Transport; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D006684:HLA-DR Antigens; D019061:src-Family Kinases; D011493:Protein Kinase C; D064546:Protein Kinase C beta