Siglec-G is a B1 cell-inhibitory receptor that controls expansion and calcium signaling of the B1 cell population

TY - JOUR

T1 - Siglec-G is a B1 cell-inhibitory receptor that controls expansion and calcium signaling of the B1 cell population

AU - Hoffmann, Anja

AU - Kerr, Sheena

AU - Jellusova, Julia

AU - Zhang, Jiquan

AU - Weisel, Florian

AU - Wellmann, Ute

AU - Winkler, Thomas H.

AU - Kneitz, Burkhard

AU - Crocker, Paul R.

AU - Nitschke, Lars

PY - 2007/7

Y1 - 2007/7

N2 - 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.

AB - 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.

KW - GENE

KW - PROTEIN-TYROSINE-PHOSPHATASE

KW - MARGINAL ZONE

KW - CD22-DEFICIENT MICE

KW - LIFE-SPAN

KW - CD22

KW - B-1 CELLS

KW - MONOCLONAL-ANTIBODIES

KW - IMMUNE-SYSTEM

KW - NEGATIVE REGULATION

U2 - 10.1038/ni1480

DO - 10.1038/ni1480

M3 - Article

C2 - 17572677

SN - 1529-2908

VL - 8

SP - 694

EP - 704

JO - Nature Immunology

JF - Nature Immunology

IS - 7

ER -