B-cell tolerance. II. Trinitrophenyl human gamma globulin-induced tolerance in adult and neonatal murine B cells responsive to thymus- dependent and independent forms of the same hapten

Abstract

When mouse spleen cells are exposed to TNP17HgG [trinitrophenylated human .gamma.-globulin] for 24 h before being immunized with TNP-SRBC [TNP-sheep erythrocytes] in Mishell-Dutton cultures, antigen-specific suppression of the TNP response is observed in cell populations previously exposed to TNP17HgG concentrations greater than 1 .mu.g/ml. In parallel cultures immunized with TNP-Brucella (TI antigen), antigen-specific suppression of the TNP response was observed at much lower tolerogen doses with 50% suppression occurring in populations previously exposed to approximately 0.01 .mu.g TNP17HgG. When the identical protocol is used with spleen cells from 6-7 day old neonates, different results are observed. In cultures immunized with TNP-SRBC or TNP-Brucella, suppression is seen at tolerogen concentrations approximately equal to those causing suppression of adult cells responsive to TNP-Brucella and less than 0.1% of those that suppress adult cells responsive to TNP-SRBC. Whereas neonatal B [bone marrow-derived] cells responsive to TD [thymus-dependent] antigens are hypersusceptible to tolerance induction as compared to adult B cells, B cells from adults and neonates that are reactive to TI [thymus-independent] form of the antigen apparently display the same level of susceptibility. This level of susceptibility is similar to that of neonatal responders to a TD antigen, i.e., the precursor cells are markedly susceptible to induction of tolerance.