Studies on immunological paralysis. XI. A comparison of the tolerogenicity in vitro of levan and type 3 pneumococcal polysaccharide

Abstract Brief exposure of mouse spleen cell suspensions to levan (LE) in vitro induced a state of stable, specific unresponsiveness in these cells, as demonstrated by LE challenge 1 – 15 days after transfer of LE‐treated cells into lethally irradiated recipients. These mice showed unimpaired responsiveness to type 3 pneumococcal polysaccharide (SIII) and sheep erythrocytes as compared with recipients of untreated cells. Suppression was attained by incubation in amounts of LE varying from 25 μg up to 10 mg/spleen equivalent and the increment in effect with rising concentrations of LE was relatively small. Tolerance induction in vitro was not dependent on the extremely high molecular weight of LE (mol. wt. 2 x 10 7 ) because it was equally demonstrable when hydrolyzed LE with a 1000‐fold reduction in average mol. wt. was used. Induction of unresponsiveness to LE could be prevented by exposure of spleen cells to anti‐mouse Fab serum prior to incubation with LE. In contrast, attempts to produce similar suppression using SIII were completely unsuccessful. It is concluded that the difference in behavior of these two thymus‐independent antigens may be a reflection of weaker overall binding of SIII to IgM receptors on B cells than is the case with LE. Consistent with this view is the demonstration that highly depolymerized LE retained the capacity to inhibit the detection of LE‐specific plaque‐forming cells, whereas SIII of similar mol. wt. had lost this property.