Unmethylated CpG motifs protect murine B lymphocytes against Fas-mediated apoptosis.
CD40 ligand (CD40L) has been shown to increase surface Fas expression and induce B cell sensitivity to Fas-dependent CD4+ Th1 cell-mediated cytotoxicity (Th1-CMC). We investigated the role of unmethylated mitogenic CpG motifs in regulating Fas-mediated apoptosis in primary murine B cells. Unmethylated CpG motifs protected CD40L-stimulated B cells from Th1-CMC and apoptosis mediated by Fas-specific antibody. Mitogenic CpG motifs downregulated Fas expression on CD40L-stimulated B cells in a time-dependent fashion. These observations suggest that Fas-mediated apoptosis requires minimum upregulation of surface Fas expression and that CpG motifs protect B cells from Fas-mediated apoptosis by decreasing surface Fas expression. Thus, these results suggest a novel mechanism for induction of Fas resistance in B cells.
Wang
Z
Z
Department of Medicine, Boston Medical Center, Massachusetts 02118, USA.
Karras
J G
JG
Colarusso
T P
TP
Foote
L C
LC
Rothstein
T L
TL
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D023201:CD40 Ligand; D019175:DNA Methylation; D015226:Dinucleoside Phosphates; D015536:Down-Regulation; D005434:Flow Cytometry; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D019014:fas Receptor / Q000502:physiology*
D023201:CD40 Ligand; D015226:Dinucleoside Phosphates; D008562:Membrane Glycoproteins; D019014:fas Receptor; C015772:CpG dinucleotide