Induced Life Extension in SLE-Model Mice by Irradiation that Selectively Eliminated CD180-Negative B Cells.

CD180 molecule, a homologue of TLR-4, expresses on mature B cells. A large number of B cells in peripheral blood express CD180 on surface. It was reported that CD180-negative B cells increase in peripheral blood from patients with autoimmune diseases such as SLE, a number of CD180-negative cells is reflected a stage of the disease, and CD180-negative cells from SLE patients produce autoantibodies. These results suggest that the CD180 expression on B cells was strongly concerned with autoimmune reaction. We previously showed that CD180-negative spleen B cells were more radiosensitive than CD180-positive cells with regard to apoptosis. In this study, we attempted to demonstrate the relationship between CD180 expression and autoimmune reaction in an animal SLE model, the NZBWF1 mice. Animals attained the criteria of disease occurrence were paired according to body weight and other conditions. One of the pair was irradiated with 4 Gy of X-rays, and the other sham-irradiated. After irradiation, the life span of the irradiated mice was significantly increased than that of the sham-irradiated mice and same as paired mice. The amount of complement C3 in peripheral blood, which decreases as the disease, of the irradiated mice was markedly higher than their sham-irradiated mice at 3 weeks after irradiation. By immunohistological examination of kidneys, number of CD180-negative cells of SLE mice increased compared with that before disease. The findings support the conception that radiation could effectively eliminate CD180-negative B cells, leading to the reduced production of autoantibodies, and thus relieve SLE symptoms. The findings suggest the possibility of practical application of radiotherapy to autoimmune diseases. CD180 molecule, a homologue of TLR-4, expresses on mature B cells. A large number of B cells in peripheral blood express CD180 on surface. It was reported that CD180-negative B cells increase in peripheral blood from patients with autoimmune diseases such as SLE, a number of CD180-negative cells is reflected a stage of the disease, and CD180-negative cells from SLE patients produce autoantibodies. These results suggest that the CD180 expression on B cells was strongly concerned with autoimmune reaction. We previously showed that CD180-negative spleen B cells were more radiosensitive than CD180-positive cells with regard to apoptosis. In this study, we attempted to demonstrate the relationship between CD180 expression and autoimmune reaction in an animal SLE model, the NZBWF1 mice. Animals attained the criteria of disease occurrence were paired according to body weight and other conditions. One of the pair was irradiated with 4 Gy of X-rays, and the other sham-irradiated. After irradiation, the life span of the irradiated mice was significantly increased than that of the sham-irradiated mice and same as paired mice. The amount of complement C3 in peripheral blood, which decreases as the disease, of the irradiated mice was markedly higher than their sham-irradiated mice at 3 weeks after irradiation. By immunohistological examination of kidneys, number of CD180-negative cells of SLE mice increased compared with that before disease. The findings support the conception that radiation could effectively eliminate CD180-negative B cells, leading to the reduced production of autoantibodies, and thus relieve SLE symptoms. The findings suggest the possibility of practical application of radiotherapy to autoimmune diseases.第39回日本免疫学会総会・学術集会、conference objec