The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/2/791/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 4, February 17, 1997 791-794

Brief Definitive Reports

Effects of Breeding Environments on Generation and Activation of Autoreactive B-1 Cells in Anti-red Blood Cell Autoantibody Transgenic Mice

Masao Murakami*, Kazuo Nakajima{ddagger}, Ken-ichi Yamazaki{ddagger}, Takehiko Muraguchi{ddagger}, Tadao Serikawa{ddagger}, and Tasuku Honjo*

From the * Department of Medical Chemistry, Kyoto University Faculty of Medicine, Sakyo-ku Yoshida, Kyoto 606, Japan; {ddagger} Institute of Laboratory Animals, Kyoto University Faculty of Medicine, Sakyo-ku Yoshida, Kyoto 606, Japan

In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B cells are deleted except for B-1 cells in the peritoneal cavity and the gut. About one-half of the auto Ab Tg mice suffer from autoimmune hemolytic anemia (AIHA) in the conventional condition. Oral administration of lipopolysaccharides activates B-1 cells and induces autoimmune symptoms in the Tg mice, suggesting that the autoimmune disease in anti-RBC autoAb Tg mice is triggered by infections. To examine the association of bacterial infections with the generation of B-1 cells and the occurrence of the autoimmune disease, we analyzed anti-RBC autoAb Tg mice bred in germ-free and specific pathogen-free conditions. In germ-free conditions, few peritoneal B-1 cells were detected, while a significant number of peritoneal B-1 cells existed in specific pathogen-free conditions. In both conditions, no mice suffered from AIHA. However, when these Tg mice were transferred to the conventional condition or injected with lipopolysaccharide, peritoneal B-1 cells expanded and some of these mice suffered from AIHA. These results clearly showed that bacterial infections are responsible for both the expansion of B-1 cells and the onset of the autoimmune disease in these Tg mice.

Address correspondence to Dr. Tasuku Honjo; Department of Medical Chemistry, Kyoto University Faculty of Medicine, Sakyo-Ku Yoshida, Kyoto 606, Japan.


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