Abstract 53

Background: The intimate communication of the CD40 receptor(CD40R) on B-lymphocytes with the CD40 ligand (CD40L) on T-lymphocytes is crucial for B-cell proliferation, differentiation, isotype switching and prevention of apoptosis in germinal centres of lymph nodes. The significance of this interaction for the immune response is obvious in patients suffering from the Hyper-IgM syndrome, where mutations in the CD40L lead to recurrent bacterial and pneumocystis carinii infections and an increased risk for autoimmune diseases and malignancies. Recently, we have shown activation of small G-proteins via tyrosine kinases in lymphocytes upon CD40R and CD40L triggering, respectively. In addition, CD40L induces activation of PLCγ, release of Ca2+ and IP3 and an activation of PKC. Here, we identify another signalling pathway initiated by CD40L stimulation.

Measurements: Biochemical determination of lipid metabolites in lymphocytes.

Results: Stimulation of T-lymphocytes via CD40L results in activation of the neutral but not an acidic sphingomyelinase. This correlates with a consumption of sphingomyelin and a release of ceramide. Activation of the neutral sphingomyelinase is independent of CD40L induced protein kinase activation as demonstrated by protein kinase inhibitors. Co-immunoprecipitation experiments exclude an association of the neutral sphingomyelinase with the CD40L.

Conclusion: The CD40L behaves as a bifunctional molecule, first, by activating B-cells via their CD40R and, second, by transmitting stimulatory signals in T-lymphocytes.

Supported by the German Research Foundation (315/6-1)