Irreversible immunological tolerance to thymus-independent antigens is restricted to the clone of B cells having both Ig and PBA receptors for the tolerogen.

Mice were tolerized to the alpha1-6 epitope of native dextran. When their spleen cells were removed and activated by LPS, they did not synthesize antibodies against the tolerogen. However, when cells from tolerant mice were treated with dextranase or left untreated in culture for 24 h they were activated by LPS to the synthesis of antibodies against the tolerogen. When 24 h tolerized lymphocytes were treated with dextranase and transferred with immunogenic doses of dextran to irradiated mice they failed to produce antibodies against the tolerogen. In contrast, cells incubated with dextran for 2 h and thereafter dextranase treated were readily immunized by dextran in the same system. It is concluded that only the B cell clones having both Ig receptors and PBA receptors for the tolerogen become irreversibly tolerized, whereas B cells having Ig receptors for a different PBA are not tolerized, but remain in a resting state, even though their Ig receptors have bound the tolerogen.