23 The Repertoire of Igg Expressing B-Cells Develops Much Slower in Preterm Than in Term Infants

Abstract

Background: Even very immature preterm infants in the first weeks of life develop a repertoire of B cells with IgG-type antigen receptors (1). Yet, the different kinetics of the postnatal evolution of B effector cells in preterm an term neonates are unknown. Hypothesis: The variable (V) region gene diversity of the IgG repertoire and the somatic diversity increases slower in preterm than in term neonates. Study design: Crossover observational study. Methods: Heavy chain V-region genes coding for the antigen binding site of the IgG-type B-cell receptor were amplified, cloned and sequenced. The diversity of the V-region gene repertoire was determined from the percentage of different amplificates in the total number of amplificates. In addition, the number of somatic mutations per V-region gene was calculated. Results: We analyzed peripheral blood samples of 8 preterm infants (GA 24–27 weeks, postnatal age 0–14 weeks) and of 16 term infants (postnatal age 0–16 weeks). In preterm infants V-region gene diversity increased slowly with postnatal age (r=0.82; p<0.000) from 30% at birth to 47% at 4 weeks, and to 82% at 12 weeks. In contrast, in term neonates already at two weeks of age diversity was higher than 80%. Furthermore the frequency of somatic mutations per V-region gene increased faster in preterm (r=0.712; p<0.004) than in term infants (r=0.83; p<0.000). Per postnatal week the accumulation of somatic mutations was three times higher in term than in preterm infants (0.12% per week vs 0.04% per week). Conclusion: In the first weeks of life both preterm and term infants respond to environmental antigens. However, preterm infants are much slower in developing an IgG repertoire. (1) Bauer K et al. Diversification of Ig heavy chain genes in human preterm neonates prematurely exposed to environmental antigens. J Immunol 2002;169:1349–1356