CD180-negative B cells play a crucial role in the development of SLE-like morbidity in NZBWF1 mice.

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