Mechanisms of B cell tolerance: I. Dynamic nature of the induction of hapten-specific unresponsiveness by hapten-conjugated pneumococcal polysaccharide.

Exposure of 2,4-dinitrophenyl (DNP)-hemocyanin-primed spleen cells to DNP-conjugated pneumococcal polysaccharide (DNP-S3) in vivo or in vitro renders such cells unresponsive to DNP-hemocyanin challenge following adoptive transfer. The unresponsiveness is hapten-specific, independent of the presence of T cells and adherent cells, and not due to either toxic effect of S3 or carry-over of tolerogenic amounts of cell-bound DNP-S3, and thus presumably represents a model of B cell tolerance. The degree of suppression induced depends upon the dose of the tolerogen and most strikingly on the duration of exposure of cells to the tolerogen. Thus 2 to 6 h exposure to DNP-S3 has an insignificant effect on anti-DNP responses, while 24 and 48 h exposures in vitro and in vivo are highly suppressive. Such a dynamic process of tolerance induction suggests a "multiple hit" phenomenon, implying the generation of suppressive signals by repeated cycles of tolerogen-receptor interactions. The process can be interrupted by removal of extracellular DNP-S3, although this does not reverse the unresponsiveness that has already been induced.