Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding

Int Immunol. 2006 Jan;18(1):59-68. doi: 10.1093/intimm/dxh349. Epub 2005 Nov 15.


CD22 functions primarily as a negative regulator of B-cell receptor signaling. The Cd22a allele has been proposed as a candidate allele for murine systemic lupus erythematosus. In this study, we explored the possible expression of aberrant forms of CD22, which differ in the N-terminal sequences constituting the ligand-binding site due to synthesis of abnormally processed Cd22 mRNA, in several Cd22a mouse strains, including C57BL/6 Cd22 congenic mice. The staining pattern of splenic B cells obtained with CY34 anti-CD22 mAb, which was expected to bind poorly to the aberrant CD22, was more heterogeneous in Cd22(a) mice than in Cd22b mice. Moreover, CD22 detected on B cells of Cd22a mice was expressed more weakly and as a smaller-sized protein, compared with Cd22b mice. Significantly, analysis with a synthetic CD22 ligand demonstrated that Cd22a mice carried a larger proportion of CD22 that was not bound by cis ligands on the B-cell surface than Cd22b mice. Finally, the study of C57BL/6 Cd22 congenic mice revealed that Cd22a B cells displayed a phenotype reminiscent of constitutively activated B cells (reduced surface IgM expression and augmented MHC class II expression), as reported for B cells expressing a mutant CD22 lacking the ligand-binding domain. Our demonstration that Cd22a B cells express aberrant forms of CD22, which can potentially deregulate B-cell signaling because of their decreased ligand-binding capacity, provides further support for Cd22a as a potential candidate allele for murine systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • B-Lymphocytes / immunology*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Genes, MHC Class II / genetics
  • Genes, MHC Class II / immunology
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Ligands
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred NZB
  • Mice, Knockout
  • RNA Processing, Post-Transcriptional / genetics
  • RNA Processing, Post-Transcriptional / immunology*
  • Sialic Acid Binding Ig-like Lectin 2 / genetics
  • Sialic Acid Binding Ig-like Lectin 2 / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*


  • Cd22 protein, mouse
  • Immunoglobulin M
  • Ligands
  • Sialic Acid Binding Ig-like Lectin 2