Macrophage depletion decreases IgG anti-DNA in cultures from (NZB x NZW)F1 spleen cells by eliminating the main source of IL-6.

We have studied the role of macrophages in the production of IgG anti-DNA autoantibodies by (NZB x NZW)F1 mice (B/W). One of the main features of the systemic lupus erythematosus (SLE)-like disease that affects these mice, is the presence of circulating IgG autoantibodies and immune complexes, which lead to renal failure and death by the age of 8-9 months. IgG autoantibodies are produced without in vitro stimulation by total spleen cells from these mice when they reach the age of 6 months. We have demonstrated that IL-6 increases the production of IgG autoantibodies in cultures of splenic purified B cells from the old B/W mice. The aim of this study was to show the involvement of macrophages in the production of IL-6 and consequently in the production of IgG anti-DNA antibodies in vitro. We show that elimination of the macrophages by different treatments led to reduction of the content of IL-6 in the supernatants as well as of IgG anti-DNA autoantibodies. Addition of fresh, splenic or peritoneal macrophages restored the production of autoantibodies in macrophage-depleted cultures from old B/W mice. There were no differences in the capacity of IL-6 production between macrophages from old or young B/W mice, but an important difference was observed between peritoneal and splenic macrophages, where the former produced much higher levels of IL-6, and consequently were more potent inducers of IgG autoantibodies. The present results reinforce the role of macrophages and IL-6 in the production of IgG anti-DNA autoantibodies in B/W mice. The implications of these results in the pathogenesis of the disease are discussed.