title: Siglec-G is a B1 cell-inhibitory receptor that controls expansion and calcium signaling of the B1 cell population.
abstract: B1 cells are an important cell population for the production of natural antibodies and for antibacterial immunoglobulin responses. Here we identified the mouse protein Siglec-G as a B1 cell inhibitory receptor. Siglec-G was expressed in a B cell-restricted way, with large amounts present in B1 cells. When overexpressed, Siglec-G inhibited B cell receptor-mediated calcium signaling. Siglec-G-deficient mice had massive expansion of the B1a cell population, which began early in development and was B cell intrinsic. Siglec-G-deficient mice had higher titers of natural IgM antibodies but not a higher penetrance of IgG autoantibodies. Siglec-G-deficient B1 cells showed a strongly enhanced calcium signaling. Our results demonstrate that Siglec-G-dependent negative regulation exists in B1 cells, which may explain the naturally muted signaling response of B1 cells.
authors.affiliation: Department of Genetics, University of Erlangen, 91058 Erlangen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Sheena
authors.initials: S
authors.lastname: Kerr
authors.forename: Julia
authors.initials: J
authors.lastname: Jellusova
authors.forename: Jiquan
authors.initials: J
authors.lastname: Zhang
authors.forename: Florian
authors.initials: F
authors.lastname: Weisel
authors.forename: Ute
authors.initials: U
authors.lastname: Wellmann
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Winkler
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kneitz
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002645:Chickens; D003001:Cloning, Molecular; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D037102:Lectins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
chemical_list: D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; D019158:N-Acetylneuraminic Acid