Induction of b cell tolerance to polysaccharides by exhaustive immunization and during immunosuppression with cyclophosphamide.

Mice immunized with an optimal (10 μg), but not suboptimal, dose of levan (LE) became specifically unresponsive to a second dose given 2–8 weeks later. No evidence which could implicate an active suppression mechanism was found. In particular (a) spleen cells from unresponsive donors did not inhibit normal cells in a transfer system; (b) equilibration of serum antibody following 2 days celomic parabiosis between LE-treated and normal mice did not impair responsiveness of the latter. It was concluded that B cells were exhausted in the absence of memory cell accumulation. LE can therefore induce specific B cell deletion, not only directly with 1 mg, but also following immunization with 10 μg. The exhaustive capacity of another polysaccharide, SIII, was found to be much weaker. Cyclophosphamide (CP) (150 mg/kg) completely suppressed the responses to LE and SIII when injected with them. Recovery following CP alone was nearly complete 2 weeks later, but simultaneous injection of an immunizing amount of LE was succeeded by dose-related specific tolerance. Total suppression followed only 100 ng LE + CP, a 10 000-fold reduction in the “high zone” tolerizing dose. The corresponding reduction in SIII experiments was only 5-fold. The times for recovery following transfer of spleen cells from donors tolerant of LE in the exhaustion and CP models were 2 and 4 weeks, respectively; periods commensurate with B cell renewal. The basis for these further differences in the tolerogenic properties of LE and SIII are discussed.