A chemical approach to the mechanism of B-lymphocyte activation. III. The B-cell-activating structure of T-independent antigens resides ultimately in the carrier.

Non-immunogenic dinitrophenyl-polymethylmethacrylate and dinitrophenyl-cellulose were rendered immunogenic by introducing, or by exposing, hydroxyl groups; i.e. hydrogen bonds. Conversely, acetylation of Ficoll yielded a polymer no longer functioning as a good carrier, and a similar result was obtained when dipole and hydrogen bond-supplying groups of polyacrylamide were replaced by more hydrophobic chains. All these findings point towards the existence of a carrier-associated lymphocyte-triggering structure. Despite the latter conclusion, the carrier need not be a polyclonal antibody inductor. The possibility of a signal not resulting in polyclonal antibody induction was tested with the system Ficoll/dinitrophenyl-Ficoll: whereas a pulse of Ficoll specifically impaired the immunogenicity of dinitrophenyl-Ficoll, it did not elicit a significant antibody level increase over background. Nevertheless, repetitive Ficoll inoculations into mice gradually increased the basal anti-trinitrophenyl antibody level, and concomitantly the anti-dinitrophenyl response to dinitrophenyl-Ficoll was specifically impaired since the anti-trinitrophenyl response to trinitrophenyl-LPS was unaffected. The two main conclusions are that (1) the ultimate lymphocyte-triggering structure resides in the carrier, and (2) the mere presence of that carrier-associated structure does not mean polyclonal antibody induction, at least under conventional test conditions (i.e. one pulse, 2 days in culture).