Department of Biology, University of Erlangen, 91058 Erlangen, Germany;
Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan;
J Immunol. 2014 Jun 1;192(11):5406-14. doi: 10.4049/jimmunol.1302875. Epub 2014 Apr 30.
Siglec-G is an inhibitory receptor on B1 cells. Siglec-G-deficient mice show a large B1 cell expansion, owing to higher BCR-induced Ca(2+) signaling and enhanced cellular survival. It was unknown why Siglec-G shows a B1 cell-restricted inhibitory function. With a new mAb we could show a comparable Siglec-G expression on B1 cells and conventional B2 cells. However, Siglec-G has a different ligand sialic acid-binding pattern on peritoneal B1 cells than on splenic B cells, and its sialic acid ligands are expressed differentially on these two B cell populations, suggesting that cis-ligand binding plays a crucial role on B1 cells. This observation was further studied by generation of Siglec-G knockin mice with a mutated ligand-binding domain. These mice show increased B1 cell numbers, increased B1 cell Ca(2+) signaling, better B1 cell survival, and changes in the B1 cell Ig repertoire. These phenotypes are very similar to Siglec-G-deficient mice. The mutation of the ligand-binding domain of Siglec-G strongly reduces the Siglec-G-IgM association on the B cell surface. Thus, Siglec-G sialic acid-dependent binding to the BCR is crucial for the B1 cell-restricted inhibitory function of Siglec-G and is regulated in an opposite way to that of the related protein CD22 (Siglec-2) on B cells.
Siglec-G 是 B1 细胞上的抑制性受体。Siglec-G 缺陷小鼠表现出较大的 B1 细胞扩增，这归因于更高的 BCR 诱导的 Ca(2+)信号和增强的细胞存活。尚不清楚为什么 Siglec-G 表现出 B1 细胞受限的抑制功能。使用一种新的 mAb，我们可以在 B1 细胞和传统的 B2 细胞上观察到可比的 Siglec-G 表达。然而，Siglec-G 在腹膜 B1 细胞上的唾液酸结合模式与在脾 B 细胞上不同，其唾液酸配体在这两个 B 细胞群体上的表达不同，表明顺式配体结合在 B1 细胞上起着至关重要的作用。这种观察结果通过生成具有突变配体结合域的 Siglec-G 敲入小鼠进一步研究。这些小鼠表现出增加的 B1 细胞数量、增加的 B1 细胞 Ca(2+)信号、更好的 B1 细胞存活以及 B1 细胞 Ig 库的变化。这些表型与 Siglec-G 缺陷小鼠非常相似。Siglec-G 配体结合域的突变强烈降低了 B 细胞表面上 Siglec-G-IgM 的结合。因此，Siglec-G 依赖于唾液酸与 BCR 的结合对于 Siglec-G 的 B1 细胞受限的抑制功能至关重要，并且以与 B 细胞上相关蛋白 CD22（Siglec-2）相反的方式受到调节。
