Tolerance as an active process.

The clonal deletion model proposed by Burnet and Lederberg and expanded by Nossal was one of the first theories concerning the nature of tolerance of self constituents. The model proposed that during the maturation of lymphocytes into immunocompetent cells, there is a sensitive differentiation stage whereby contact wth antigen results in specific inactivation of the cell. Experimental evidence indicates that neonatal or immature B lymphocytes are indeed different from adult lymphocytes in their extreme sensitivity to tolerance induction even at low antigen concentrations and with antigens that are normally immunogenic. The present study examines the mechanism of this tolerance phenomenon by determining whether or not tolerance of immature B cells is an active process and what specific interactions can induce this event. We used various putative inhibitors of tolerance induction in the splenic focus assay which examines the tolerance susceptibility of individual B cells. The results suggest that tolerance requires protein synthesis and that this process is initiated only after a minimum threshold affinity of binding occurs between antigen and cell-surface receptor with subsequent receptor interlinkage.