Alteration of idiotypic connectivity in prenatally tolerized neonatal mice

Abstract

Prenatal tolerization with trinitrobenzenesulphonic acid (TNBS) leads to expansion of trinitrophenyl (TNP)-specific B cells, the majority of which become refractory to stimulation during postnatal development. One possible explanation could be that they belong to the repertoire of naturally activated B cells which are limited in expansion after antigenic stimulation due to a high degree of idiotypic connectivity. To evaluate this hypothesis, 59 thymus- and 490 spleen-derived B-cell hybridomas from 6-day-old prenatally untreated and prenatally TNBS-treated mice were tested for reactivity against 33 arbitrarily chosen clones derived from the same fusions, 17 being derived from control and 16 from tolerized litters. Two major points could be deduced: (1) Idiotypic connectivity, including connectivity of TNP- and anti-TNP-reactive monoclonal antibodies (MoAb), was maintained after prenatal tolerization. This accounted for thymus- and spleen-derived MoAb. (2) Only TNP- and anti-TNP-reactive MoAb derived from prenatally untreated and prenatally tolerized mice displayed significantly distinct idiotypic profiles. Differences were pronounced, especially with thymus-derived MoAb. Thus, TNP-specific B cells in prenatally tolerized newborns do not behave like B cells of adult mice stimulated by external antigen, but rather like a part of the naturally activated, idiotypically connected B-cell repertoire of the newborn. This could explain B-cell unresponsiveness at older age as a consequence--at least partly--of their high idiotypic connectivity.