References
Query Results -- Details
MGI Accession ID: MGI:3611413
J Number: J:104168
Other Accession IDs:
Title: Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding.
Authors: Nitschke L; Lajaunias F; Moll T; Ho L; Martinez-Soria E; Kikuchi S; Santiago-Raber ML; Dix C; Parkhouse RM; Izui S
Journal: Int Immunol
Volume: 18
Issue: 1
Date: 2006 Jan
Year: 2006
Pages: 59-68
Review Status: Peer Reviewed
Abstract:
CD22 functions primarily as a negative regulator of B-cell receptor signaling. The Cd22(a) 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 Cd22(a) 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 Cd22(b) mice. Moreover, CD22 detected on B cells of Cd22(a) mice was expressed more weakly and as a smaller-sized protein, compared with Cd22(b) mice. Significantly, analysis with a synthetic CD22 ligand demonstrated that Cd22(a) mice carried a larger proportion of CD22 that was not bound by cis ligands on the B-cell surface than Cd22(b) mice. Finally, the study of C57BL/6 Cd22 congenic mice revealed that Cd22(a) 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 Cd22(a) 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 Cd22(a) as a potential candidate allele for murine systemic lupus erythematosus.
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