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

B细胞表面表达抑制性受体CD22和Siglec-G，可抑制B细胞的反应。E3泛素连接酶cullin 3是一种与CD22相互作用的蛋白，调节B细胞表面CD22的表达。在CD22和Siglec-G基因突变的小鼠中，研究了这两种基因在自发自身免疫中的作用。在B细胞慢性淋巴细胞白血病(B-CLL)小鼠模型中，分析了Siglec-G在B-CLL中的作用。当小鼠缺乏Siglec-G时，B-CLL的发展要早得多。这一点将在第三个资助期跟进。CD22在生发中心反应中的作用也将被研究，因为初步结果显示CD22 KO GC B细胞具有竞争劣势。

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.