The Yaa mutation promoting murine lupus causes defective development of marginal zone B cells
| Autor: | Eduardo Martinez-Soria, Thomas Wirth, Isabelle Semac, Shozo Izui, Thomas Moll, Nabila Ibnou-Zekri, Dragan Marinkovic, Eri Amano, Lars Nitschke, Hirofumi Amano |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Lymphopenia/genetics/immunology ddc:616.07 Transgenes/immunology medicine.disease_cause Mice Receptors Complement 3d/biosynthesis immune system diseases Y Chromosome Immunology and Allergy Transgenes skin and connective tissue diseases Cells Cultured Trinitrobenzenes/immunology Mice Knockout Mutation Stem Cells CD22 Cell Differentiation Marginal zone Antigens T-Independent Lupus Nephritis Phenotype Lupus Nephritis/ genetics/ immunology/pathology medicine.anatomical_structure Trinitrobenzenes Injections Intravenous Down-Regulation/genetics/immunology Spleen/immunology/metabolism/pathology Antigens T-Independent/administration & dosage/immunology Transgene Cell Differentiation/genetics/immunology Immunology B-Lymphocyte Subsets Kruppel-Like Transcription Factors Down-Regulation Mice Transgenic Biology Lymphopenia medicine Animals Secretion Lymphocyte Count Stem Cells/immunology/pathology B cell B-Lymphocyte Subsets/ immunology/metabolism/ pathology Y Chromosome/ genetics/ immunology Gene Expression Regulation/immunology Autoantibody Mice Mutant Strains Transcription Factors/biosynthesis/deficiency/genetics Mice Inbred C57BL Gene Expression Regulation Immunoglobulin M Immunoglobulin M/biosynthesis/genetics Receptors Complement 3d Spleen Transcription Factors |
| Zdroj: | Journal of Immunology Journal of Immunology, Vol. 170, No 5 (2003) pp. 2293-2301 |
| ISSN: | 0022-1767 |
| Popis: | The accelerated development of systemic lupus erythematosus (SLE) in BXSB male mice is associated with the presence of an as yet unidentified mutant gene, Yaa (Y-linked autoimmune acceleration). In view of a possible role of marginal zone (MZ) B cells in murine SLE, we have explored whether the expression of the Yaa mutation affects the differentiation of MZ and follicular B cells, thereby implicating the acceleration of the disease. In this study, we show that both BXSB and C57BL/6 Yaa mice, including two different substrains of BXSB Yaa males that are protected from SLE, displayed an impaired development of MZ B cells early in life. Studies in bone marrow chimeras revealed that the loss of MZ B cells resulted from a defect intrinsic to B cells expressing the Yaa mutation. The lack of selective expansion of MZ B cells in diseased BXSB Yaa males strongly argues against a major role of MZ B cells in the generation of pathogenic autoantibodies in the BXSB model of SLE. Furthermore, a comparative analysis with mice deficient in CD22 or expressing an IgM anti-trinitrophenyl/DNA transgene suggests that the hyperreactive phenotype of Yaa B cells, as judged by a markedly increased spontaneous IgM secretion, is likely to contribute to the enhanced maturation toward follicular B cells and the block in the MZ B cell generation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|