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Norway

PMID:19103880  

B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase.

Annaiah Cariappa | Hiromu Takematsu | Haoyuan Liu | Sandra Diaz | Khaleda Haider | Cristian Boboila | Geetika Kalloo | Michelle Connole | Hai Ning Shi | Nissi Varki | Ajit Varki | Shiv Pillai
The Journal of experimental medicine | 2009

We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B cell development, signaling, and immunological tolerance. Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically removes acetyl moieties from the 9-OH position of alpha2-6-linked sialic acid, exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell development, and spontaneously develop antichromatin autoantibodies and glomerular immune complex deposits. The 9-O-acetylation state of sialic acid regulates the function of CD22, a Siglec that functions in vivo as an inhibitor of BCR signaling. These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage.

Pubmed ID: 19103880

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM032373
  • Agency: NIGMS NIH HHS, United States
    Id: GM32373
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL057345
  • Agency: NHLBI NIH HHS, United States
    Id: P01HL057345
  • Agency: NIAID NIH HHS, United States
    Id: AI069458
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI069458
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM032373
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI064930
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK043351
  • Agency: NIAID NIH HHS, United States
    Id: AI064930

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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U2OS (tool)

RRID:CVCL_0042

Cell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)

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