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

J Exp Med. 2009 Jan 16;206(1):125-38. doi: 10.1084/jem.20081399. Epub 2008 Dec 22.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Acetylesterase
  • Animals
  • Antibodies, Antinuclear / blood
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / physiology
  • Blotting, Western
  • Bone Marrow Cells / cytology
  • Carboxylic Ester Hydrolases / genetics
  • Carboxylic Ester Hydrolases / metabolism*
  • Cell Count
  • Cell Differentiation / physiology*
  • Glomerulonephritis / genetics
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Models, Biological
  • Mutation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Receptors, Antigen, B-Cell / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialic Acid Binding Ig-like Lectin 2 / metabolism
  • Sialic Acids / metabolism
  • Signal Transduction / physiology*
  • Spleen / cytology

Substances

  • Antibodies, Antinuclear
  • Cd22 protein, mouse
  • Receptors, Antigen, B-Cell
  • Sialic Acid Binding Ig-like Lectin 2
  • Sialic Acids
  • Carboxylic Ester Hydrolases
  • Acetylesterase
  • sialate O-acetylesterase
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Ptpn6 protein, mouse