Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation.
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.
Moll
Thomas
T
Department of Pathology and Immunology, Centre Médical Universitaire, Geneva, Switzerland.
Martinez-Soria
Eduardo
E
Santiago-Raber
Marie-Laure
ML
Amano
Hirofumi
H
Pihlgren-Bosch
Maria
M
Marinkovic
Dragan
D
Izui
Shozo
S
D000744:Anemia, Hemolytic, Autoimmune / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis; D051741:Kruppel-Like Transcription Factors; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D014157:Transcription Factors / Q000276:immunology; D019076:Transgenes / Q000276:immunology; D014998:Y Chromosome / Q000235:genetics*
C465395:4C8 antigen, human; D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D007075:Immunoglobulin M; D051741:Kruppel-Like Transcription Factors; C498818:Sp6 protein, mouse; D014157:Transcription Factors; D004247:DNA