Siglec-G is a B1 cell-inhibitory receptor that controls expansion and calcium signaling of the B1 cell population.
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.
Hoffmann
Anja
A
Department of Genetics, University of Erlangen, 91058 Erlangen, Germany.
Kerr
Sheena
S
Jellusova
Julia
J
Zhang
Jiquan
J
Weisel
Florian
F
Wellmann
Ute
U
Winkler
Thomas H
TH
Kneitz
Burkhard
B
Crocker
Paul R
PR
Nitschke
Lars
L
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
D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; D019158:N-Acetylneuraminic Acid