Interaktionen von CD22 mit Milchglykoproteinen und mögliche Auswirkungen auf die Regulation der B-Zell-Aktivierung
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|Other Titles:||Interactions of CD22 with milk glycoproteins and potential effects on theregulation of B-cell activation||Authors:||Bock, Nadine||Supervisor:||Kelm, Sørge||1. Expert:||Kelm, Sørge||2. Expert:||Boehm, Günther||Abstract:||
The development of the neonatal immune system is well balanced by breast milk components leading to an appropriate maturation of the immune system. Poorly balanced support of the developing immune system may lead to autoimmune diseases or allergies. Different properties of milk formula components could be the reason for deviations from this balance. Little is known about the molecular mechanisms leading to effects of milk components on the immune system. One mechanism known to regulate B-cell receptor-mediated cell activation is the inhibitory effect of CD22, which sialic acid-dependent interaction on the B-cell surface seems to be critical for its negative regulatory function. The results presented in this work provide a differentiated perspective for the regulation of the immune system by milk glycoproteins/-peptides and clearly demonstrate species-dependent differences between milk proteins. Human caseins were identified as potential inhibitors of the sialic acid-dependent interaction of CD22 with IgM. They inhibited better than undigested camel caseins, human whey proteins and bovine caseins. Proteolytic digestion of caseins reduced the inhibitory potencies, whereas the inhibitory potencies of digested whey proteins increased. Most of the sialylated proteins and CD22-specific binding partners were identified in human caseins by lectin blotting. After affinity chromatography of human caseins, caseins (k-casein) and the MFGM proteins clusterin and lactoferrin were identified as isolated ligands of CD22. In B-cell activation assays the Ca-mobilisation was clearly reduced in presence of digested caseins and whey proteins, but sialylation appears to reduce these effects strongly. Obviously, the interaction of milk glycoproteins/-peptides lead to different effects than the sialic acid derivative BPC-Neu5Ac, which reduces the inhibitory function of CD22. This finding indicate a mechanism independent of the sialic acid binding site for the milk glycoproteins/-peptides.
|Keywords:||CD22; milk glykoproteins, B-cell activation, breast milk, milkproteins/-peptides, cow, camel, immune regulation, sialic acids, newborn||Issue Date:||25-Aug-2004||URN:||urn:nbn:de:gbv:46-diss000010330||Institution:||Universität Bremen||Faculty:||FB2 Biologie/Chemie|
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