The ligand-binding domain of Siglec-G is crucial for its selective inhibitory function on B1 cells.
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.
Department of Biology, University of Erlangen, 91058 Erlangen, Germany;
Stefan
S
Hutzler
Department of Biology, University of Erlangen, 91058 Erlangen, Germany;
Lamia
L
Özgör
Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan;
Yuko
Y
Naito-Matsui
BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79108 Freiburg, Germany; Intitute for Biology III, Department of Molecular Immunology, Faculty of Biology, University of Freiburg, D-79108 Freiburg, Germany; Max Planck Institute for Immunobiology and Epigenetics, D-79108 Freiburg, Germany; and.
Kathrin
K
Kläsener
Department of Biology, University of Erlangen, 91058 Erlangen, Germany; Nikolaus-Fiebiger Center for Molecular Medicine, University of Erlangen, 91058 Erlangen, Germany.
Thomas H
TH
Winkler
BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79108 Freiburg, Germany; Intitute for Biology III, Department of Molecular Immunology, Faculty of Biology, University of Freiburg, D-79108 Freiburg, Germany; Max Planck Institute for Immunobiology and Epigenetics, D-79108 Freiburg, Germany; and.
Michael
M
Reth
Department of Biology, University of Erlangen, 91058 Erlangen, Germany; lars.nitschke@fau.de.
Lars
L
Nitschke
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D020013:Calcium Signaling / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D037102:Lectins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
D007075:Immunoglobulin M; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse