Age-dependent responsiveness to interleukin-6 in B lymphocytes from a systemic lupus erythematosus-prone (NZB x NZW)F1 hybrid.

The cellular mechanisms for the production of IgG anti-DNA antibodies were studied. Culture of T and B cells from old (NZB x NZW)F1 mice led to the production of IgG anti-DNA antibodies. We found that direct cell contact was partly necessary for the production of IgG anti-DNA antibodies. Fixation of the T cells showed that lymphokines were largely responsible for the antibody synthesis. Antibodies to mouse interleukin-6 (IL-6) inhibited the production of these antibodies in the T-B cell coculture. Human IL-6 could induce small "resting" B cells from the old (NZB x NZW)F1 mice to produce IgG anti-DNA antibodies in a dose-dependent fashion. The response was inhibited by an anti-human IL-6 monoclonal antibody. Large or small B cells from young (B/W)F1 mice or Balb/c mice were not induced by IL-6 to antibody production. Therefore, the capacity of the B/W mice to produce the IgG anti-DNA antibodies correlated with the ability of the B cells to respond to IL-6 and with the age at which the mice begin to have signs of the disease.