Division of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany.
Front Immunol. 2018 Dec 3;9:2820. doi: 10.3389/fimmu.2018.02820. eCollection 2018.
CD22 and Siglec-G are members of the Siglec family. Both are inhibitory co-receptors on the surface of B cells and inhibit B-cell receptor induced signaling, characterized by inhibition of the calcium mobilization and cellular activation. CD22 functions predominantly as an inhibitor on conventional B cells, while Siglec-G is an important inhibitor on the B1a-cell subset. These two B-cell Siglecs do not only inhibit initial signaling, but also have an important function in preventing autoimmunity, as double deficient mice develop a lupus-like phenotype with age. Siglecs are characterized by their conserved ability to bind terminal sialic acid of glycans on the cell surface, which is important to regulate the inhibitory role of Siglecs. While CD22 binds α2,6-linked sialic acids, Siglec-G can bind both α2,6-linked and α2,3-linked sialic acids. Interestingly, ligand binding is differentially regulating the ability of CD22 and Siglec-G to control B-cell activation. Within the last years, quite a few studies focused on the different functions of B-cell Siglecs and the interplay of ligand binding and signal inhibition. This review summarizes the role of CD22 and Siglec-G in regulating B-cell receptor signaling, membrane distribution with the importance of ligand binding, preventing autoimmunity and the role of CD22 beyond the naïve B-cell stage. Additionally, this review article features the long time discussed interaction between CD45 and CD22 with highlighting recent data, as well as the interplay between CD22 and Galectin-9 and its influence on B-cell receptor signaling. Moreover, therapeutical approaches targeting human CD22 will be elucidated.
CD22 和 Siglec-G 是 Siglec 家族的成员。它们都是 B 细胞表面的抑制性共受体，抑制 B 细胞受体诱导的信号转导，其特征是抑制钙动员和细胞激活。CD22 主要作为常规 B 细胞的抑制剂发挥作用，而 Siglec-G 是 B1a 细胞亚群的重要抑制剂。这两种 B 细胞 Siglec 不仅抑制初始信号转导，而且在预防自身免疫方面具有重要功能，因为双缺陷小鼠随着年龄的增长会发展出狼疮样表型。Siglecs 的特征是它们能够结合细胞表面糖链末端唾液酸的保守能力，这对于调节 Siglecs 的抑制作用很重要。虽然 CD22 结合α2,6 连接的唾液酸，但 Siglec-G 可以结合α2,6 连接和α2,3 连接的唾液酸。有趣的是，配体结合以不同的方式调节 CD22 和 Siglec-G 控制 B 细胞激活的能力。在过去的几年中，相当多的研究集中在 B 细胞 Siglecs 的不同功能以及配体结合和信号抑制的相互作用上。这篇综述总结了 CD22 和 Siglec-G 在调节 B 细胞受体信号转导、膜分布以及配体结合的重要性、预防自身免疫和 CD22 在幼稚 B 细胞阶段之外的作用。此外，本文综述还介绍了 CD45 和 CD22 之间长期讨论的相互作用，重点介绍了最近的数据，以及 CD22 和半乳糖凝集素-9 之间的相互作用及其对 B 细胞受体信号转导的影响。此外，还将阐明针对人 CD22 的治疗方法。
