Sialic acid binding domains of CD22 are required for negative regulation of B cell receptor signaling

J Exp Med. 2002 May 6;195(9):1199-205. doi: 10.1084/jem.20011796.


CD22, a negative regulator of B cell antigen receptor signaling, binds glycoconjugates terminating in alpha2, 6 sialic acid. The physiological ligand(s) for CD22 remain unknown. We asked whether the sialic acid binding domains are necessary for CD22 to function as a negative regulator. We generated two mutants that lack sialic acid binding activity and expressed them in a novel CD22(-/-) murine B cell line. Anti-IgM activated B cells expressing either CD22 mutant had greater Ca(2+) responses than cells expressing wild-type CD22. Each variant also had reduced CD22 tyrosine phosphorylation and Src homology 2 domain-containing protein tyrosine phosphatase-1 association. These data suggest that the alpha2, 6 sialic acid ligand binding activity of CD22 is critical for its negative regulatory functions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • Binding Sites
  • Calcium Signaling / physiology*
  • Cell Adhesion Molecules*
  • Cell Line
  • DNA Primers
  • Gene Expression Regulation / immunology
  • Genetic Vectors
  • Humans
  • Lectins*
  • Mice
  • Mutagenesis, Site-Directed
  • N-Acetylneuraminic Acid / metabolism*
  • Receptors, Antigen, B-Cell / immunology*
  • Recombinant Proteins / metabolism
  • Retroviridae / genetics
  • Sialic Acid Binding Ig-like Lectin 2
  • Signal Transduction / immunology
  • Transfection


  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD22 protein, human
  • Cd22 protein, mouse
  • Cell Adhesion Molecules
  • DNA Primers
  • Lectins
  • Receptors, Antigen, B-Cell
  • Recombinant Proteins
  • Sialic Acid Binding Ig-like Lectin 2
  • N-Acetylneuraminic Acid