Activation of the Janus kinase 3-STAT5a pathway after CD40 triggering of human monocytes but not of resting B cells.
CD40/CD40 ligand interactions play a key role in the immune responses of B lymphocytes, monocytes, and dendritic cells. The signal transduction events triggered by cross-linking of the CD40 receptor have been widely studied in B cell lines, but little is known about signaling following CD40 stimulation of monocytes and resting tonsillar B cells. Therefore, we studied the CD40 pathway in highly purified human monocytes and resting B cells. After CD40 triggering, a similar activation of the NF-kappaB (but not of the AP-1) transcription factor complex occurred in both cell preparations. However, the components of the NF-kappaB complexes were different in monocytes and B cells, because p50 is part of the NF-kappaB complex induced by CD40 triggering in both monocytes and B cells, whereas p65 was only induced in B cells. In contrast, although the Janus kinase 3 tyrosine kinase was associated with CD40 molecules in both monocytes and resting B cells, Janus kinase 3 phosphorylation induction was observed only in CD40-activated monocytes, with subsequent induction of STAT5a DNA binding activity in the nucleus. These results suggest that the activation signals in human B cells and monocytes differ following CD40 stimulation. This observation is consistent with the detection of normal CD40-induced monocyte activation in patients with CD40 ligand+ hyper IgM syndrome in whom a defect in CD40-induced B cell activation has been reported.
Institut National de la Santé et de la Recherche Médicale, Unité 429, Hôpital Necker-Enfants Malades, Paris, France.
P
P
Revy
C
C
Hivroz
G
G
Andreu
P
P
Graber
C
C
Martinache
A
A
Fischer
A
A
Durandy
D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000502:physiology*; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007399:Interphase / Q000276:immunology; D053616:Janus Kinase 3; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D019013:CD40 Antigens; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D017346:Protein Serine-Threonine Kinases