CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms

Nat Immunol. 2004 Oct;5(10):1078-87. doi: 10.1038/ni1121. Epub 2004 Sep 19.


The interaction of CD22 with alpha2,6-linked sialic acid ligands has been widely proposed to regulate B lymphocyte function and migration. Here, we generated gene-targeted mice that express mutant CD22 molecules that do not interact with these ligands. CD22 ligand binding regulated the expression of cell surface CD22, immunoglobulin M and major histocompatibility complex class II on mature B cells, maintenance of the marginal zone B cell population, optimal B cell antigen receptor-induced proliferation, and B cell turnover rates. However, CD22 negative regulation of calcium mobilization after B cell antigen receptor ligation, CD22 phosphorylation, recruitment of SHP-1 to CD22 and B cell migration did not require CD22 ligand engagement. These observations resolve longstanding questions regarding the physiological importance of CD22 ligand binding in the regulation of B cell function in vivo.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / physiology*
  • Antigens, Differentiation, B-Lymphocyte / physiology*
  • B-Lymphocytes / physiology*
  • Cell Adhesion Molecules / physiology*
  • Cell Movement
  • Lectins / physiology*
  • Ligands
  • Lymphocyte Activation
  • Mice
  • N-Acetylneuraminic Acid / metabolism*
  • Receptors, Antigen, B-Cell / physiology
  • Sialic Acid Binding Ig-like Lectin 2


  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • Cd22 protein, mouse
  • Cell Adhesion Molecules
  • Lectins
  • Ligands
  • Receptors, Antigen, B-Cell
  • Sialic Acid Binding Ig-like Lectin 2
  • N-Acetylneuraminic Acid