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International Immunology Advance Access originally published online on August 31, 2004
International Immunology 2004 16(10):1487-1495; doi:10.1093/intimm/dxh150
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© 2004 The Japanese Society for Immunology

Auto-reactive B cells against peripheral antigen, desmoglein 3, escape from tolerance mechanism

Takayuki Ota1,2, Miyo Aoki-Ota1, Kazuyuki Tsunoda1,3, Kouji Simoda4, Takeji Nishikawa1, Masayuki Amagai1 and Shigeo Koyasu2,5

1 Department of Dermatology, 2 Department of Microbiology and Immunology, 3 Department of Dentistry and Oral Surgery and 4 Laboratory Animal Center, Keio University School of Medicine, Tokyo 160-8582, Japan
5 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan

Correspondence to: S. Koyasu; E-mail: koyasu{at}sc.itc.keio.ac.jp

To examine the mechanism of B cell tolerance against natural peripheral self-antigen, we generated transgenic mice expressing IgM specific for desmoglein 3 (Dsg3) from AK7 monoclonal antibody which itself does not induce blisters. Dsg3 is mainly expressed on stratified squamous epithelium and is the target antigen of an autoimmune bullous disease, pemphigus vulgaris. Transgenic B cells reactive to Dsg3 were observed in the spleen and lymph node. Although these B cells are autoreactive, they did not develop into B1 B cells. These B cells were functionally competent and anti-Dsg3 IgM was detected in the serum and on the keratinocyte cell surface. These results indicate that auto-reactive B cells against peripheral antigen (Dsg3) are able to develop in the presence of Dsg3 but are ignored by the immune system.

Keywords: autoimmunity, B1 B cell, pemphigus vulgaris, peripheral tolerance, transgenic mouse

Transmitting editor: T. Kurosaki


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