Prevention of autoimmune symptoms in autoimmune-prone mice by elimination of B-1 cells

Our recent studies on an autoantlbody-transgenic mouse line demonstrated that peritoneal B-1 cells are responsible for autoimmune symptoms. However, whether B-1 cells In the peritoneum are generally Involved in the pathogenesis of autoimmune disease remains controversial. To test the possible Involvement of peritoneal B-1 cells In autoimmune symptoms of autoimmune-prone NZB mice, we eliminated the peritoneal cells by hypotonic shock with repeated l.p. Injection of distilled water every 7 days Into neonatal or 8-week-old NZB mice. By this treatment, B-1 cells, which self-renew within the peritoneal cavity, are expected to be preferentially eliminated, while other peritoneal cells can be easily supplied from bone marrows after this treatment. Indeed, in distilled water-treated old NZB mice, the number of B-1 cells decreased in spleen as well as In lamina propria of the gut but the numbers of conventional B cells and T cells did not change. Moreover, the production of autoantibodies against erythrocytes significantly decreased and the occurrence of autoimmune hemolytic anemia was reduced In 12-month-old treated NZB mice. Similarly, the elimination of peritoneal cells of NZB/NZW (NZB/W) F1 mice by water injection decreased antl-DNA IgG antibodies In the sera and reduced the pathological changes of the kidney. These results suggest that peritoneal B-1 cells may be a source of autoantibody-produclng cells In autoimmune diseases of NZB and NZB/W F1 mice