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

Martinez-Soria, Eduardo
Pihlgren-Bosch, Maria
Marinkovic, Dragan
Published in 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/mortalityAnimalsAntibodies, Antinuclear/*biosynthesisAntigens, CD/genetics/immunologyB-Lymphocyte Subsets/*immunology/metabolismCells, CulturedDNA/*immunologyErythrocytes/*immunologyFemaleImmunoglobulin M/biosynthesisKruppel-Like Transcription Factors*Lymphocyte Activation/geneticsMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, Transgenic*MutationTranscription Factors/immunologyTransgenes/immunologyY Chromosome/*genetics
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Other version: http://www.jimmunol.org/cgi/reprint/174/2/702.pdf
PMID: 15634889
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