Mechanisms of B cell tolerance

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.