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

Moll, Thomas; Martinez-Soria, Eduardo; Santiago-Raber, Marie-Laure; Amano, Hirofumi; Pihlgren-Bosch, Maria; Marinkovic, Dragan; Izui, Shozo

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Title		Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation
Authors		Moll, Thomas Martinez-Soria, Eduardo Santiago-Raber, Marie-Laure Amano, Hirofumi Pihlgren-Bosch, Maria Marinkovic, Dragan Izui, Shozo
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/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		DOI: 10.4049/jimmunol.174.2.702 PMID: 15634889
Full text		Article - Limited access to UNIGE Other version: http://www.jimmunol.org/cgi/reprint/174/2/702.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Citation (ISO format)		MOLL, Thomas et al. Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation. In: Journal of Immunology, 2005, vol. 174, n° 2, p. 702-709. https://archive-ouverte.unige.ch/unige:11478