Induction of antibody response by antigen conjugates and E. coli lipopolysaccharide in mice tolerant to dextran B-512.

Three groups of mice were made tolerant to dextran (Dex) with one of three schedules: a) an immunogenic dose of 10 micrograms three times a week for 26 weeks; b) an immunogenic dose of 50 micrograms three times a week for two weeks, and c) a single tolerogenic dose of 10 mg. Prior to tolerance induction, continuous administration of 10 micrograms Dex induced a predominantly IgM antibody response. The tolerant mice were then challenged with immunogenic doses of the dextran conjugates Dex-Salmonella typhi (Dex-S. typhi) and Dex-sheep red blood cells (Dex-SRBC), and with E. coli lipopolysaccharide (LPS). IgM and IgG responses were compared in each group. Immunogenic dextran alone did not induce a response in the 1 tolerant mice. The response induced by Dex-S. typhi or Dex-SRBC was low but LPS induced an elevated anti-Dex SFC in the three groups of resistant mice. The antibody responses were not affected by pretreatment of antigen with dextranase. Loss of tolerance was more pronounced in mice made tolerant by continuous stimulation as compared to mice made tolerant by a single large dose of antigen. Thus, LPS is able to induce specific responses from B cells of tolerant animals. Furthermore, the level of response was dependent on the toleration schedule.