Tolerance as an active process

Abstract

The clonal deletion model, proposed by Burnet and Lederberg and expanded by Nossal, was one of the 1st theories concerning the nature of tolerance to self constituents. The model proposed that during the maturation of lymphocytes into immunocompetent cells, there is a sensitive differentiation stage whereby contact with antigen results in specific inactivation of the cell. Experimental evidence indicates that neonatal, or immature B lymphocytes, are different from adult lymphocytes due to their extreme sensitivity to tolerance induction. This is evident even at low antigen concentrations and with antigens that are normally immunogenic. The mechanism of this tolerance phenomenon was examined by determining whether or not tolerance of immature [mouse] B cells is an active process, and what specific interactions can induce this event. Various putative inhibitors of tolerance induction were used in the splenic focus assay, which examines the tolerance susceptibility of individual B cells. Tolerance probably requires protein synthesis; this process probably is initiated only after a minimum threshold affinity of binding between antigen and cell surface receptor, with subsequent receptor interlinkage.