Search

Mature B cell expressing CD180 molecules was first reported showing a protective effect against radiation- or dexamethasone-induced apoptosis in vitro. CD180 is a homologue of toll-like receptor (TLR) 4 and a pivotal regulator of cell proliferation and death. In SLE patients, number of CD180-negative B cells showed to increase in peripheral blood, and the change in the number of CD180-negative B cells appeared to be associated with the activity of SLE. In addition, such negative cells collected from SLE patients produced autoantibodies in vitro. We previously showed that the radiosensitivity of CD180-negative cells was greater than that of CD180-positive cells in vivo. In SLE-model NZBWF1 mice, we also reported the increase in number of CD180-negative B cells in parallel with development of SLE morbidity, the production of autoantibodies by CD180-negative cells, and pathogenesis of lupus-like nephritis caused by CD180-negative cells. We therefore, here, examine the effects of Xray-irradiation targeted CD180-negative B cells in NZBWF1 female mice. After the onset of symptoms, mice were paired according to their conditions. In each pair, one was irradiated with 4 Gy, and the other was sham-irradiated. Compared to the sham-irradiated mice, the number of CD180-negative cells was significantly decreased, the mean life span was markedly extended, and the nephritis and the morbid conditions were remarkably suppressed in irradiated mice. These findings suggest that radiation could effectively eliminate CD180-negative B cells, resulting in reduction of autoantibody production, and thus relieve SLE-like morbidity in SLE-model NZBWF1 mice. The findings also suggest a possibility that the radiotherapy for autoimmune diseases associated with the expression of CD180-negative cells, such as SLE and Sögren syndrome, might be a novel candidate for practical application., The 16th International Congress of Radiation Research (ICRR2019）

Toll-like receptors appear to play an important role in the pathogenesis of lupus-like nephritis in mice. In human and mouse, CD180 is a homologue of TLR4. In SLE patients, the number of CD180-negative B cells in peripheral blood changes in parallel with disease activity. In the present study using NZBWF1 mice, the population of splenic CD180-negative B cells increased with progression of renal lesions and aging. These cells produced both anti-dsDNA and histone antibodies; the peripheral blood levels of anti-dsDNA antibody increased markedly with aging. B cells infiltrating into renal lesions were CD180-negative and produced anti-dsDNA antibody. Considered together, these findings indicate that CD180-negative B cells contribute significantly to development of SLE-like morbidity in NZBWF1 mice by autoantibody production.

CD180 molecule is a homologue of TLR-4 and expresses on mature B cells. The molecule shows a protective effect against radiation- or dexamethasone-induced apoptosis in vitro. CD180 is a key regulator of cell proliferation and death. We previously showed CD180-negative spleen B cells exhibited sensitivity for radiation-induced apoptosis compared with CD180-positive cells in vivo. In SLE patients, the number of CD180-negative B cells increased in peripheral blood, and appeared to be associated with the activity of SLE. In addition, such negative cells collected from SLE patients produced autoantibodies in vitro. We previously reported CD180-negative B cells might lead to development of SLE morbidity in SLE-model mouse, NZBWF1. In the present study, we attempted to examine the effects of X-ray irradiation on CD180-negative B cells in NZBWF1 female mice. After irradiation, the mean life span of the irradiated mouse group was significantly extended compared with that of the sham-irradiated one. In addition, the latency to the development of grade three-proteinuria in irradiated mouse is significantly longer than in sham-irradiated one. The amount of complement C3 in peripheral blood of the irradiated mouse was sustained at normal level, while that of sham-irradiated mouse was markedly decreased at 3 weeks after sham-irradiation. These findings suggest that radiation could effectively eliminate CD180-negative B cells, leading to reduction of autoantibody production, and thus relieve SLE symptoms. The findings also suggest a possibility that the radiotherapy into autoimmune diseases associated with the expression of CD180-negative cells might be a novel practical application., 15th International Congress of Immunology (第15回国際免疫学会議).

The CD180 molecule is a receptor of LPS on mature B cell and a homologue of TLR 4, and regulates TLR 4 negatively. The molecule has a protective effect against radiation- or dexamethasone-induced apoptosis in vitro. Antibody-mediated cross-linkingof CD180 induces a strong proliferative response, and secondary cross-linking of surface IgM induces B cell apoptosis in vitro. CD180 is thus a key regulator of proliferation and cell death. However, few studies regarding the functional mechanism of the CD180 molecule associated with radiation-induced apoptosis have been reported in vivo. In the present study, we have examined the effect of irradiation on the expression patterns of CD180 of spleen cell and compared with that of CD19 and CD21 on B cell in vivo. Spleens of BALB/c female mice at 7-8 weeks were removed after whole body-irradiation of 4 Gy. Histochemical analysis demonstrated that CD180-positive lymphocytes significantly increased in number at 6 h after irradiation compared with both at 3 h and 0 h. In contrast, no significant change of the numbers of lymphocytes positive for CD19 or CD22 was at 0 h, 3 h, and 6 h after irradiation. Flow cytometric analysis showed that the percentage of CD180-presenting B cells increased at 6 h after irradiation than that at 0 h. As the expression of CD180 was increased dependently on radiation dose from 0 Gy to 10 Gy and on the level of apoptosis with histochemical analysis, double staining for TUNEL and CD180 was performed to clarify the relationship of the expression patterns between apoptosis and CD180. The double staining showed that the number of CD180-positive cells positive for TUNEL was significantly less than that of CD180-negative cells positive for TUNEL at 6 h after irradiation. These results suggested that CD180- positive B lymphocytes were resistant to apoptosis induced by irradiation in vivo., 第41回日本免疫学会学術集会

The Role of CCR7-Ligands in Developing Experimental Autoimmune Encephalomyelitis

Systemic lupus erythematosus (SLE) is a disease usually caused by aberrant self-tolerance, in which self-reactive T and B cells are activated, resulting in production of various autoimmune antibodies. A recent study demonstrated that TLRs appear to play a role in the production of autoimmune antibodies. CD180 is a homologue of TLR 4 and a key regulator of proliferation and cell death expressing on B lymphocyte. In SLE patients, the population of CD180-negative B cells in the peripheral blood is significantly increased and changes in parallel with SLE disease activity. In the present study using NZBWF1 mice, we explored the role of CD180-negative B cells in the development of systemic autoimmune disorders and in the pathogenesis of lupus-like nephritis. The results showed that the population of CD180-negative B cells in spleen increased with age and well correlated with grades of renal lesions. In addition, CD180-negative B cells obtained from the spleen produced anti-dsDNA antibody in vitro. The amount of the antibody in peripheral blood of the mouse remarkably increased with advancing age. These results indicated that the CD180-negative B cells significantly participate in the progression of SLE-like morbid condition. In further experiments, infiltrated B cells into the renal lesion were characterized to be CD180-negative and proved to produce anti-dsDNA antibody in vitro. In conclusion, the present study revealed that CD180-negative B cells play a crucial role in the development of SLE-like morbidity in experimental NZBWF1 mice., 第40回日本免疫学会学術集会

CD180 molecule, a homologue of TLR-4, expresses on mature B cells. CD180-negative B cells in peripheral blood in SLE patients were reported to increase and to reflected the activity of SLE, in addition, they produce autoantibodies in vitro. These results suggest that CD180 expression was strongly associated with autoimmune reaction. We previously showed that CD180-negative spleen B cells exhibited greater radiosensitive than CD180-positive cells. In this study, we examined the radiation effects on CD180-negative B cells using an animal SLE model, the NZBWF1 female mice. After the onset of the early symptoms of protein urea, mice were paired according to the degree of the symptoms and the body weight. One of the pair was irradiated by 4 Gy, and the other sham-irradiated. The mean life span of the irradiated mice was significantly extended compared with that of the sham-irradiated mice and the same results were obtained when comparing with the paired mice. The amount of complement C3 in peripheral blood of the irradiated mice was sustained markedly at higher levels than that of sham-irradiated mice at 3 weeks after irradiation. Immunohistological examination of kidneys showed increased number of CD180-negative B cells after the onset of the early symptom. The findings indicate the possibility that radiation could eliminate effectively CD180-negative B cells, leading to reduction of autoantibody production, and thus relieve SLE symptoms. The findings also suggest the possibility of the effectiveness of practical application of radiotherapy into autoimmune diseases associated with the expression of CD180-negative cells., 第14回国際免疫学会議

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、