Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B.
The B cell-associated surface molecule CD40 functions to regulate B cell responses. Cross-linking CD40 on B cells can lead to homotypic cell adhesion, IL-6 production, and, in combination with cytokines, to Ig isotype switching. Tyrosine kinase activity is increased shortly after engagement of this receptor. Little is known about how the very early events induced by CD40 cross-linking link to cellular responses. In this study, we demonstrate that nuclear factor (NF)-kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines. The activation is rapid and is mediated through a tyrosine kinase-dependent pathway. The complexes detected in electrophoretic mobility shift assays contain p50, p65 (RelA), c-Rel, and most likely other components. By using transient transfection assays, we found that cross-linking CD40 supports NF-kappa B-dependent gene expression. Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites.
Berberich
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Department of Microbiology, University of Washington, Seattle 98195.
Shu
G L
GL
Clark
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EA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D019013:CD40 Antigens; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology; D010084:Oxidation-Reduction; D014066:Palatine Tonsil / Q000166:cytology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D022762:CCAAT-Enhancer-Binding Proteins; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases