Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Front Immunol. 2018 Oct 2;9:2276. doi: 10.3389/fimmu.2018.02276. eCollection 2018.
B cells express various inhibitory co-receptors including CD22, CD72, and Siglec-G. These receptors contain immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic region. Although many of the inhibitory co-receptors negatively regulate BCR signaling by activating SH2-containing protein tyrosine phosphatase 1 (SHP-1), different inhibitory co-receptors have distinct functional properties. CD22, Siglec-G, and CD72 preferentially regulate tonic signaling in conventional B cells, B-1 cell homeostasis, and development of lupus-like disease, respectively. CD72 recognizes RNA-related lupus self-antigen Sm/RNP as a ligand. This ligand recognition recruits CD72 to BCR in Sm/RNP-reactive B cells thereby suppressing production of anti-Sm/RNP autoantibody involved in the pathogenesis of lupus. In contrast, Siglec-G recognizes α2,3 as well as α2,6 sialic acids whereas CD22 recognizes α2,6 sialic acid alone. Because glycoproteins including BCR are dominantly glycosylated with α2,3 sialic acids in B-1 cells, Siglec-G but not CD22 recruits BCR as a ligand specifically in B-1 cells, and regulates B-1 cell homeostasis by suppressing BCR signaling in B-1 cells. Thus, recognition of distinct ligands determines functional properties of different inhibitory B cell co-receptors.
B 细胞表达各种抑制性共受体，包括 CD22、CD72 和 Siglec-G。这些受体在细胞质区域包含免疫受体酪氨酸抑制基序（ITIM）。尽管许多抑制性共受体通过激活含 SH2 的蛋白酪氨酸磷酸酶 1（SHP-1）来负调控 BCR 信号，但不同的抑制性共受体具有不同的功能特性。CD22、Siglec-G 和 CD72 分别优先调节常规 B 细胞的基础信号、B-1 细胞的稳态和狼疮样疾病的发展。CD72 识别 RNA 相关狼疮自身抗原 Sm/RNP 作为配体。这种配体识别将 CD72 募集到 Sm/RNP 反应性 B 细胞中的 BCR，从而抑制参与狼疮发病机制的抗 Sm/RNP 自身抗体的产生。相比之下，Siglec-G 识别 α2,3 以及 α2,6 唾液酸，而 CD22 仅识别 α2,6 唾液酸。由于包括 BCR 在内的糖蛋白在 B-1 细胞中主要被 α2,3 唾液酸化糖基化，因此 Siglec-G 而不是 CD22 特异性地将 BCR 作为配体募集到 B-1 细胞中，并通过抑制 B-1 细胞中的 BCR 信号来调节 B-1 细胞的稳态。因此，不同配体的识别决定了不同抑制性 B 细胞共受体的功能特性。
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