Tolerance induction during ontogeny II. Distinct unresponsive states in immature mice question the generality of clonal abortion

摘要

AbstractMultivalent trinitrophenyl (TNP) conjugates of both human γ‐globulin (HGG) and bovine serum albumin (BSA) are capable of inducing hapten‐specific unresponsiveness in neonatal mice, as assessed by challenge with TNP on thymus‐dependent carriers. When such mice are challenged with TNP on thymus‐independent carriers, however, only TNP‐HGG‐ but not TNP‐BSA‐treated mice are found to be substantially unresponsive to the hapten. Moreover, unresponsiveness induced by BSA, but not HGG, as a carrier was associated with the presence of antigen‐specific suppressor cells. Thus, contrary to predictions made by defendants of the classical clonal abortion hypothesis, functional deletion of hapten‐specific B cells appears to depend on the nature of the hapten‐carrier complex. This conclusion is supported by B cell‐precursor frequency estimates indicating that the number of hapten‐specific precursor cells is significantly lower in TNP‐HGG‐treated mice, but remains unaltered in TNP‐BSA‐treated mice relative to the precursor frequency in untreated animals. While it remains a formal possibility that the differences in tolerogenicity seen between the two carriers can be interpreted in terms of a difference in serum half‐life, we favor the interpretation that the distinction lies in molecular aspects of the carrier, which allow for differences in antigen h