Tolerance inducibility and the elicitation of autoantibodies by LPS in aged NZB mice.

Correlation between tolerance inducibility to human IgG and the elicitation of anti-erythrocyte autoantibodies by LPS was investigated in NZB mice. At first, tolerance inducibility to human IgG was examined in various ages of the mice. Straight relationship was found between the age of mice and tolerance inducibility; the older mice became, the more difficult it became to induce tolerance. This age-related change was also shown at the level of B lymphocytes. When LPS was injected into tolerogen-resistant, aged mice, anti-erythrocyte autoantibodies were elicited. On the other hand, autoantibodies were never detected in younger NZB mice or other strains of comparable aged mice. From these results, it is assumed that similar mechanisms are operating in the escape from self-tolerance and the resistance to tolerance to heterologous antigens, thus self-reactive B lymphocytes gradually appear with the age of NZB nice in which the resistance to tolerance induction become apparent.