Background: The CD40 receptor on B-lymphocytes and its ligand gp39 on T-cells regulate proliferation and maturation of B-cells and antibody class switching. Deficient signaling via CD40 due to mutations of the ligand gp39 causes the Hyper-IgM syndrome, an X-linked immunodeficiency.
Aim: Identification of signal transduction events triggered by CD40 crosslinking.
Methods: Immunoprecipition, kinase-, Ras-assays, synthesis of diacylglycerol.
Results: Stimulation of Daudi B-cells by a monoclonal CD40 antibody resulted in an activation of the small G-protein p21Ras and the downstream target MAP-Kinase. Activation of Ras could be partially blocked by Herbimycin A or Calphostin, preincubation with both inhibitors completely prevented Ras activation. In accordance, CD40 triggering increased kinase activity of the src-kinases Fyn and Blk and induced synthesis of diacylglycerol. A potential molecule mediating the activation of Ras upon CD40 triggering is Vav, which displayed increased tyrosine phosphorylation and physical association with Ras after CD40 stimulation.
Conclusion: Stimulation of B-lymphocytes via CD40 results in a signaling cascade from src-kinase and phospholipases to Vav, Ras and MAP-Kinase, which might be important in mediating the biological effects after CD40 receptor engagement.
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Brenner, B., Gulbins, E. & Linderkamp, O. Signaling Functions of the CD40 Receptor 36. Pediatr Res 40, 521 (1996). https://doi.org/10.1203/00006450-199609000-00059
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DOI: https://doi.org/10.1203/00006450-199609000-00059