The importance of sialoglycans for lymphocyte development and function

唾液聚糖是淋巴细胞表面丰富的聚糖结构。它们作为Siglec受体或选择素的配体，但在文献中也描述了更一般的功能。该项目建立了具有B细胞特异性或T细胞特异性Cmas缺失的小鼠，Cmas是一种编码唾液聚糖合成中关键酶的基因。这些B细胞或T细胞缺乏唾液聚糖的小鼠在次级淋巴器官中显示出相应淋巴细胞群的损失。可以证明，在这两种情况下，诱导这些唾液多糖缺乏淋巴细胞凋亡参与。在Cmas缺陷B细胞中激活caspase 8表明fas受体触发的外源性凋亡途径被激活。浆细胞上有多唾液酸和双唾液酸的表达。二唾液酸缀合物是由ST8Sia6酶产生的。因此，我们开发了一种新的St8Sia6缺陷小鼠，以进一步分析二唾液酸偶联物对这些细胞类型的作用。在下一个资助期内，将完成对B细胞特异性Cmas缺陷小鼠B细胞缺陷机制的分析。Cmas在浆细胞和抗体反应中的作用将通过使用cre小鼠在B细胞成熟过程中进行随后的删除来检验。我们将详细研究T细胞特异性Cmas缺陷小鼠的T细胞缺陷。二唾液酸和7,9 o -乙酰化在浆细胞功能和T细胞功能中的作用将通过新建立的St8Sia6缺陷和Casd1条件下的KO小鼠进行分析。

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 di-sialic 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.