en
Scientific article
English

Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation

Published inThe Journal of immunology, vol. 174, no. 2, p. 702-709
Publication date2005
Abstract

An as-yet-unidentified mutation, Y-linked autoimmune acceleration (Yaa), is responsible for the accelerated development of lupus-like autoimmune syndrome in mice. In view of a possible role for Yaa as a positive regulator of BCR signaling, we have explored whether the expression of the Yaa mutation affects the development and activation of transgenic autoreactive B cells expressing either 4C8 IgM anti-RBC or Sp6 IgM anti-DNA. In this study, we show that the expression of the Yaa mutation induced a lethal form of autoimmune hemolytic anemia in 4C8 transgenic C57BL/6 mice, likely as a result of activation of 4C8 anti-RBC autoreactive B cells early in life. This was further supported, although indirectly, by increased T cell-independent IgM production in spleens of nontransgenic C57BL/6 mice bearing the Yaa mutation. In contrast, Yaa failed to induce activation of Sp6 anti-DNA autoreactive B cells, consistent with a lack of increased IgM anti-DNA production in nontransgenic C57BL/6 Yaa mice. Our results suggest that Yaa can activate autoreactive B cells in a BCR-dependent manner, related to differences in the form and nature of autoantigens.

Keywords
  • Anemia, Hemolytic, Autoimmune/*genetics/immunology/mortality
  • Animals
  • Antibodies, Antinuclear/*biosynthesis
  • Antigens, CD/genetics/immunology
  • B-Lymphocyte Subsets/*immunology/metabolism
  • Cells, Cultured
  • DNA/*immunology
  • Erythrocytes/*immunology
  • Female
  • Immunoglobulin M/biosynthesis
  • Kruppel-Like Transcription Factors
  • *Lymphocyte Activation/genetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • *Mutation
  • Transcription Factors/immunology
  • Transgenes/immunology
  • Y Chromosome/*genetics
Citation (ISO format)
MOLL, Thomas et al. Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation. In: The Journal of immunology, 2005, vol. 174, n° 2, p. 702–709. doi: 10.4049/jimmunol.174.2.702
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ISSN of the journal0022-1767
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