Studies on immunological paralysis. X. Cellular characteristics of the induction and loss of tolerance to levan (polyfructose).

The induction and loss of tolerance to native and depolymerized fractions of levan, a thymus-independent antigen, have been studied in (DBA/1×CBA-T6T6)F1 mice by a direct plaque-forming cell (PFC) assay. Tolerance following 1 mg native levan began to break by 80 days, whereas mice remained specifically unresponsive 150 days after 10 mg. Effects attributable to long persistence of antigen have been demonstrated. The following main features of levan tolerance were established by transfer of spleen cells to 900 R-irradiated recipients: (1) the induction period is very short—less than 24 hours. (2) No detectable immunity accompanies or precedes induction. (3) The fall in immunogenicity with reduction in molecular weight (mol. wt) of levan is not accompanied by loss of tolerogenicity. An effectively tolerogenic, non-immunogenic fraction (mol. wt<10,000) was found. (4) There is no rapid loss of tolerance following cell transfer (reactivity is only regained after 50 days), arguing against the existence of tolerant cells in this model. As these results and those from corresponding investigations with SIII and HGG all show major dissimilarities, it is considered imprudent to base generalizations concerning the nature of B cell tolerance on studies with only one type of antigen. Whether or not two different kinds of specific unresponsiveness might be implicated with these cells is discussed.