The Ligand-Binding Domain of Siglec-G Is Crucial for Its Selective Inhibitory Function on B1 Cells
Hutzler S, Özgör L, Naito-Matsui Y, Klaesener K, Winkler T, Reth M, Nitschke L (2014)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2014
Journal
Publisher: AMER ASSOC IMMUNOLOGISTS
Book Volume: 192
Pages Range: 5406-5414
Journal Issue: 11
Abstract
Siglec-G is an inhibitory receptor on B1 cells. Siglec-G-deficient mice show a large B1 cell expansion, owing to higher BCR-induced Ca2+ 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 Ca2+ 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.
Authors with CRIS profile
Lamia Özgör
Professur für Genetik
Thomas Winkler
Professur für Genetik
Lars Nitschke
Professur für Genetik
Involved external institutions
Japan (JP)
Germany (DE)How to cite
APA:
Hutzler, S., Özgör, L., Naito-Matsui, Y., Klaesener, K., Winkler, T., Reth, M., & Nitschke, L. (2014). The Ligand-Binding Domain of Siglec-G Is Crucial for Its Selective Inhibitory Function on B1 Cells. Journal of Immunology, 192(11), 5406-5414. https://doi.org/10.4049/jimmunol.1302875
MLA:
Hutzler, Stefan, et al. "The Ligand-Binding Domain of Siglec-G Is Crucial for Its Selective Inhibitory Function on B1 Cells." Journal of Immunology 192.11 (2014): 5406-5414.
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