Scientific article

The Yaa mutation promoting murine lupus causes defective development of marginal zone B cells

Published inThe Journal of immunology, vol. 170, no. 5, p. 2293-2301
Publication date2003

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.

  • Animals
  • Antigens, T-Independent/administration & dosage/immunology
  • B-Lymphocyte Subsets/ immunology/metabolism/ pathology
  • Cell Differentiation/genetics/immunology
  • Cells, Cultured
  • Down-Regulation/genetics/immunology
  • Gene Expression Regulation/immunology
  • Immunoglobulin M/biosynthesis/genetics
  • Injections, Intravenous
  • Kruppel-Like Transcription Factors
  • Lupus Nephritis/ genetics/ immunology/pathology
  • Lymphocyte Count
  • Lymphopenia/genetics/immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Mutation
  • Receptors, Complement 3d/biosynthesis
  • Spleen/immunology/metabolism/pathology
  • Stem Cells/immunology/pathology
  • Transcription Factors/biosynthesis/deficiency/genetics
  • Transgenes/immunology
  • Trinitrobenzenes/immunology
  • Y Chromosome/ genetics/ immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
AMANO, Hirofumi et al. The Yaa mutation promoting murine lupus causes defective development of marginal zone B cells. In: The Journal of immunology, 2003, vol. 170, n° 5, p. 2293–2301. doi: 10.4049/jimmunol.170.5.2293
Updates (1)
ISSN of the journal0022-1767

Technical informations

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