Pathogenesis of lupus-like nephritis through autoimmune antibody produced by CD180-negative B lymphocytes in NZBWF1 mouse

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.

► Splenic CD180-negative B cells increased with the level of renal lesions and aging in NZBWF1 mice.
► They produced anti-dsDNA and -histone antibodies.
► Anti-dsDNA Ab levels in the blood increased markedly with aging.
► B cells infiltrating into renal lesions exhibited CD180-negative phenotype and produced anti-dsDNA antibody.
► These cells evoked SLE-like morbidity by auto-Ab production.