Action of persistent administration of a hapten with a reactive group (TNBS) and mono-or divalent conjugates of hapten to molecules without other reactive groups on anti-TNP-LPS response.

The intrinsic tolerization mechanisms of the B cell have been postulated either at the level of membrane receptor blockade, before the appearance of membrane receptors, or more intracellularly. For the first possibility a certain multivalence or epitope/hapten density of the antigen molecule is required. Tolerance has been induced by free haptens that possess a reactive group, but haptens lacking such a reactive group may not necessarily be tolerized. We studied the effect on a possible response to trinitrophenyl-lipopolysaccharide (TNP-LPS) by persistent stimulation of immature Swiss mice with: a free hapten containing a reactive group (trinitrobenzenesulfonic acid of TNBS), the low M.W. trinitrophenyl (TNP)-glycine conjugate, and dinitrophenyl (DNP)-polyethylene glycol conjugates; the M.W. of polyethylene glycol being 6,000, 20,000 and 35,000 respectively. Persistent injection of TNBS hapten profoundly tolerated the response to TNP-LPS, whereas the administration of TNP-glycine and DNP-polyethylene glycol conjugates not only fails to tolerate the response, but might stimulate it. Possible explanations for these results are discussed; the tolerogenicactivity of TNBS is ascribed to its binding to another receptor or membrane component, thus impairing "capping" formation by the specific receptor. Alternatively, by acting more intracellularly, TNBS may inhibit the B-cell maturation/differentiation. It would be interesting to find out whether the other conjugates, which are stimulant, could also be tolerated when inoculated for a very long period of time, as has been shown to happen with many antigens administered in immunogenic doses for several months.