Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding
| Autor: | Liza Ho, Frédéric Lajaunias, Carolin Dix, Eduardo Martinez-Soria, Lars Nitschke, Shozo Izui, Shuichi Kikuchi, Thomas Moll, R. Michael E. Parkhouse, Marie-Laure Santiago-Raber |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
medicine.drug_class
Sialic Acid Binding Ig-like Lectin 2 Immunology Genes MHC Class II Congenic ddc:616.07 Signal Transduction/genetics/*immunology Biology Monoclonal antibody Ligands Immunoglobulin M/genetics/immunology Mice Lupus Erythematosus Systemic/genetics/immunology immune system diseases hemic and lymphatic diseases medicine Immunology and Allergy Animals Lupus Erythematosus Systemic RNA Processing Post-Transcriptional Alleles Mice Knockout B-Lymphocytes/*immunology MHC class II B-Lymphocytes Mice Inbred BALB C Mice Inbred C3H Systemic lupus erythematosus Mice Inbred NZB RNA Processing Post-Transcriptional/genetics/*immunology CD22 Antigens CD22/genetics/*immunology SIGLEC General Medicine Ligand (biochemistry) medicine.disease Molecular biology Phenotype Genes MHC Class II/genetics/immunology Gene Expression Regulation Immunoglobulin M biology.protein Gene Expression Regulation/genetics/*immunology Signal Transduction |
| Zdroj: | International Immunology, Vol. 18, No 1 (2006) pp. 59-68 |
| ISSN: | 0953-8178 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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