CpG oligodeoxynucleotides rescue BKS-2 immature B cell lymphoma from anti-IgM-mediated growth inhibition by up-regulation of egr-1.
Cross-linking of the IgM antigen receptor on an immature B cell lymphoma (BKS-2) induces growth arrest and apoptosis. This is accompanied by down-regulation of the immediate early genes, egr-1 and c-myc, and a reduction in NF-kappaB activity. Anti-IgM-induced growth arrest and apoptosis of this murine B cell lymphoma were prevented by oligodeoxynucleotides (ODN) containing the CpG motif, which are also known to be stimulatory for mature and immature B cells. The CpG but not non-CpG ODN rescued BKS-2 cells from anti-IgM-mediated growth inhibition by up-regulation of egr-1 and c-myc expression as well as by restoring NF-kappaB activity. Interestingly, changes in egr-1 expression occurred more rapidly than in c-myc expression. Also the c-myc levels remained high up to 6 h after addition of the anti-IgM, which was also the time until which the addition of CpG could be delayed without affecting its ability to provide complete protection. This CpG-induced rescue of B lymphoma cells was blocked by antisense egr-1 ODN, suggesting that the expression of egr-1 is important for the effects of CpG ODN on the growth and survival of BKS-2 cells.
Han
S S
SS
Department of Microbiology and Immunology, and Sanders-Brown Research Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
Chung
S T
ST
Robertson
D A
DA
Chelvarajan
R L
RL
Bondada
S
S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D051766:Early Growth Response Protein 1; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D016259:Genes, myc; D006131:Growth Inhibitors / Q000502:physiology*; D017874:Immediate-Early Proteins; D007075:Immunoglobulin M / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D006131:Growth Inhibitors; D017874:Immediate-Early Proteins; D007075:Immunoglobulin M; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C044203:anti-IgM