Postnatal B cell development: influence of trinitrobenzenesulfonic acid treatment during pregnancy.

Prenatal treatment with a reactive hapten may be well suited for analyzing the establishment of self tolerance because the hapten binds ubiquitously to proteins and cells and persists for a long period in the developing organism. Based on this consideration, pregnant BALB/c mice were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS), searching for differences in 2,4,6-trinitrophenyl (TNP) responsiveness in their offspring as compared to litters of untreated mice. The frequency of TNP-specific T-independent B cells of litters from TNBS-treated mothers was very low at birth and remained below 10% of controls until the age of 42 days. On the contrary, in 8-day-old prenatally TNBS-treated litters, the frequency of TNP-specific T-dependent B cells was higher than in controls. Expansion of TNP-specific B cells after antigenic stimulation of control mice started at the age of 3-4 weeks and expansion rates increased with age, while in prenatally TNBS-treated mice, significant expansion rates were seen at the age of 2 weeks only. Yet, after restimulation with TNP-lipopolysaccharide or with a TNP-anti-TNP conjugate, but not after restimulation with TNP-ovalbumin, similar numbers of plaque-forming cells (PFC) were observed with spleen cells of prenatally untreated and TNBS-treated mice, the latter revealing an exceptional predominance of IgG PFC. Thus, TNP-specific B cells were not deleted, but prenatal TNBS treatment resulted in an altered composition of TNP-specific B cell subpopulations, their regulation differing qualitatively from the one observed in prenatally untreated mice.