International Immunology Advance Access originally published online on November 15, 2005
International Immunology 2006 18(1):59-68; doi:10.1093/intimm/dxh349
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Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding
1 Department of Genetics, University of Erlangen, 91058 Erlangen, Germany
2 Department of Pathology and Immunology, University Medical Center, CMU, 1211 Geneva 4, Switzerland
3 Gulbenkian Institute for Science, Oeiras, Portugal
Correspondence to: S. Izui; E-mail: shozo.izui{at}medecine.unige.ch
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 Cd22a 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.
Keywords: Systemic lupus erythematosus, Siglec, CD22 ligand, Autoimmune diseases