P2 - The importance of sialoglycans for lymphocyte development and function
Sialoglycans are abundant glycan structures on the surface of lymphoyctes. They act as ligands for Siglec receptors or selectins, but also more general functions are described in the literature. This project has established mice with a B cell-specific or T cell-specific deletion of Cmas, a gene encoding for a crucial enzyme in sialoglycan synthesis. These mice with B cells, or respectively T cells, lacking sialoglycans showed a loss of the respective lymphocyte population in secondary lymphatic organs. It could be demonstrated that in both cases induction of apoptosis in these sialoglycan deficient lymphocytes is involved. Activated caspase 8 in Cmas-deficient B cells indicates activation of extrinsic apoptosis pathways triggered by the Fas-receptor. Poly-sialic and disialic acid expression on plasma cells was found. Di-sialic acid conjugates are generated by the enzyme ST8Sia6. Therefore, a new St8Sia6-deficient mouse was developed, to analyse the role of di-sialic acid conjugates further on these cell types. In the next funding period, the analysis of the mechanism of the B cell defect of the B cell-specific Cmas-deficient mouse will be finished. The role of Cmas in plasma cells and antibody responses will be examined, by using cre mice for a later deletion during B cell maturation. The T cell defect in T cell-specific Cmas-deficient mice will be examined in detail. The role of di-sialic acid and 7,9-O-acetylation in plasma cell function and T cell function will be analyzed with the help of the newly established St8Sia6-deficient and with Casd1 conditional KO mice.