Development of a method for regulation of auto-reactive B cells using transgenic mouse carrying genes encoding an anti-self-erythrocyte antibody.

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In order to identify and analyze auto-reactive B lymphocytes those involved in pathogenesis of auto-immune diseases, and to elucidate mechanism of their activation, we developed transgenic mouse system carrying genes encoding an anti-self-erythrocyte antibody and thus almost all the B lymphocytes in the transgenic mice are programd to produce the anti-self-erythrocyte antibody. By analyzing the transgenic mice, we found the following things.1. B lymphocytes are hardly detected in most of peripheral lymphatic tissues such as spleen or peripheral blood due to the elimination of self-reactive B lymphocytes. Hoerver, almost normal number of CD5^+ lymphocytes is found only in the abdominal cavity and the lamina propria of gastro-intestinal mucosa.2. Approximately half of the transgenic mouse individuals spontaneously suffered from auto-immune hemolytic anemia caused by the auto-antibody produced by the activated CD5^+ B lymphocytes in the abdominal cavity.3. When lipopolysaccharide (LPS) was orally administrated to non-anemic transgenic mice, they showed quite resembled symptoms with the spontaneously occurred anemia by activation of CD5^+ B lymphocytes in the gastro-intestine and abdominal cavity. However, they were not activated by LPS administrated by intra-muscular or intra-venous injection.4. CD5^+ B lymphocytes in the abdominal cavity died by apoptosis when the erythrocytes, i.e., the antigen itself, were injected. By repeated injection of erythrocytes into the abdominal cavity, the affected mice were recovered from anemia.These results indicate, in summary, that activation of CD5^+ B lymphocytes in the gastro-intestine and abdominal cavity is important for the onset of auto-immune diseases, and that auto-reactive B lymphocytes can be eliminated by their contact with auto-antigen. Our research clearly elucidated onset mechanism of auto-immune disease at least some part, and found a way of possible treatment of the diseases.