Induction of the transcription factors NF-kappa B, AP-1 and NF-AT during B cell stimulation through the CD40 receptor.
To address elements that might uniquely characterize CD40 mediated signaling, the nuclear expression of three transcription factors was evaluated following B cell stimulation by CD40L and by anti-Ig antibody. Cross-linked CD40L was found to induce nuclear expression of NF-kappa B, AP-1 and NF-AT with a time course and intensity similar to that produced by anti-Ig. Examination of NF-kappa B in more detail demonstrated that the CD40 mediated expression of DNA binding complexes correlated with induction of trans-activating activity which again attained similar levels following cross-linking of CD40 and slg. Despite the marked similarity in transcription factor induction triggered through CD40 and slg, differences in the intracellular signaling pathways utilized were apparent in that protein kinase C (PKC) depletion did not affect CD40 mediated induction of NF-kappa B even as induction by anti-Ig was abolished. These results suggest that a 'final common pathway' or convergence of transcription factor induction may exist for two distinct receptors, each of which is individually capable of triggering cell cycle progression, despite the use of separate intracellular signaling pathways that differ at the level of PKC. Although transcription factor induction was similar for CD40L and anti-Ig early on, subtle differences in expressed NF-kappa B and AP-1 nucleoprotein complexes were apparent at 24 h. Such differences may play a role in determining the variant effects on B cells of stimulation through these two receptors.
Francis
D A
DA
Department of Pathology, Boston University Medical Center, MA 02118, USA.
Karras
J G
JG
Ke
X Y
XY
Sen
R
R
Rothstein
T L
TL
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D016827:CD8 Antigens / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005434:Flow Cytometry; D017930:Genes, Reporter / Q000235:genetics; D007140:Immunoglobulin Fab Fragments; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes / Q000032:analysis; D011493:Protein Kinase C / Q000502:physiology; D011961:Receptors, Fc / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D007140:Immunoglobulin Fab Fragments; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011961:Receptors, Fc; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D023201:CD40 Ligand; D011493:Protein Kinase C