B cell tolerance. I. Analysis of hapten-specific unresponsiveness induced in vitro in adult and neonatal murine spleen cell populations.

The cellular mechanisms and tolerogen dose requirements of hapten-specific unresponsiveness induced in vitro by using 2,4,6-trinitrophenyl human gamma-globulin (TNP17HgG) were analyzed in adult and neonatal murine splenocytes. Tolerance induction in both cell populations was found to be independent of non-B cell effects including BAtheta-positive cells, Ly 2.2-positive cells, adding or reducing the number of macrophages, and large excesses of HgG. The tolerance induced was specific and not "infectious", further excluding a role for suppressor T cells. Neonatal splenic B cells were rendered tolerant by doses of TNP17HgG 1000-fold less than those required to produce similar tolerance in splenic B cells from adults. These findings support the concept of functional clonal abortion as a mechanism for producing tolerance to self antigens.