

Other version: http://www.jimmunol.org/cgi/reprint/174/2/702.pdf
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Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation |
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Published in | The Journal of immunology. 2005, vol. 174, no. 2, p. 702-709 | |
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 | |
Identifiers | PMID: 15634889 | |
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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 https://archive-ouverte.unige.ch/unige:11478 |