The role of Siglec proteins in B cell activation and autoimmunity (04)

Siglec 蛋白在 B 细胞激活和自身免疫中的作用 (04)

• 批准号: 243104538
• 金额: --
• 依托单位: Department Biologie
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/243104538?language=en
• 关键词: role; Siglec; proteins; cell; activation

B cells express CD22 and Siglec-G as inhibitory receptors on the cell surface, which can suppress B cell responses. The E3 ubiquitin ligase cullin 3 was identified as a CD22-interacting protein, which regulates the CD22 surface expression on B cells. The role of CD22 and Siglec-G in spontaneous autoimmunity was studied in mice with mutations in both genes. The role of Siglec-G in B cell chronic lymphocytic leukemia (B-CLL) was analysed in a B-CLL mouse model. B-CLL developed much earlier, when the mice were deficient for Siglec-G. This will be followed up in the third funding period. The role of CD22 in germinal centre responses will also be examined, as preliminary results have shown a competitive disadvantage of CD22 KO GC B cells.

B细胞表达作为细胞表面上的抑制性受体的CD 22和Siglec-G，其可以抑制B细胞应答。E3泛素连接酶cullin 3是一种与CD 22相互作用的蛋白，可调节B细胞表面CD 22的表达。在两种基因都有突变的小鼠中研究了CD 22和Siglec-G在自发性自身免疫中的作用。在B-CLL小鼠模型中分析Siglec-G在B细胞慢性淋巴细胞白血病（B-CLL）中的作用。当小鼠缺乏Siglec-G时，B-CLL发展得更早。这将在第三个供资期继续进行。由于初步结果显示CD 22 KO GC B细胞的竞争劣势，因此还将检查CD 22在生发中心反应中的作用。