Apoptosis and nucleosomes.

Drs Berden and Koutouzov presented evidence that nucleosomes are antigens in lupus pathogenesis and that apoptotic cells are the source of nucleosomes. Berden's group measured persistence of circulating nucleosomes and nucleosome-antibody complexes in autoimmune mice and demonstrated nucleosomal deposition in skin of SLE patients as well as in renal lesions. Koutouzov reported that anti-nucleosomes are among the earliest autoantibodies in MRL+/+ mice, appearing several weeks before anti-DNA antibodies. Treatment of the mice with a pro-apoptotic drug, taxotere, accelerated autoantibody production and development of lesions. Herrmann proposed that persistent immunization results from reduced dead cell clearance and reduced production of immunosuppressive cytokines by defective scavenger macrophages. He also described accumulation of apoptotic cells in germinal follicles in SLE patients and attachment of nuclear antigens that are produced in apoptosis to the surface of follicular dendritic cells. Apoptosis-derived nucleosomes may be important in both the immunizing and effector arms of pathogenesis.