Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation

Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2500-5. doi: 10.1073/pnas.0807207106. Epub 2009 Feb 6.

Abstract

CD22 is an inhibitory coreceptor on the surface of B cells that attenuates B cell antigen receptor (BCR) signaling and, therefore, B cell activation. Elucidating the molecular mechanisms underlying the inhibitory activity of CD22 is complicated by the ubiquity of CD22 ligands. Although antigens can display CD22 ligands, the receptor is known to bind to sialylated glycoproteins on the cell surface. The propinquity of CD22 and cell-surface glycoprotein ligands has led to the conclusion that the inhibitory properties of the receptor are due to cis interactions. Here, we examine the functional consequences of trans interactions by employing sialylated multivalent antigens that can engage both CD22 and the BCR. Exposure of B cells to sialylated antigens results in the inhibition of key steps in BCR signaling. These results reveal that antigens bearing CD22 ligands are powerful suppressors of B cell activation. The ability of sialylated antigens to inhibit BCR signaling through trans CD22 interactions reveals a previously unrecognized role for the Siglec-family of receptors as modulators of immune signaling.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Carbohydrate Sequence
  • Cell Line
  • Humans
  • Ligands
  • Lymphocyte Activation / immunology*
  • Molecular Sequence Data
  • N-Acetylneuraminic Acid / chemistry*
  • Sialic Acid Binding Ig-like Lectin 2 / chemistry
  • Sialic Acid Binding Ig-like Lectin 2 / immunology*
  • Signal Transduction

Substances

  • Ligands
  • Sialic Acid Binding Ig-like Lectin 2
  • N-Acetylneuraminic Acid