Human neonatal B cell immunity differs from the adult version by conserved Ig repertoires and rapid, but transient response dynamics

The human infant B cell system is considered premature or impaired. Here we show that neonates have mature and fully functional B cell subsets as seen in adults, albeit with distinct transcriptional programs providing accelerated responsiveness to T cell independent and T cell dependent stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into antibody secreting cells, thereby presumably limiting memory B cell formation. The neonatal Ig-repertoire is highly variable, but conserved, showing 8% recurrent B cell receptor (BCR) clonotypes shared between neonates. Our study demonstrates that neonatal B cells are neither premature nor impaired, but differ from their adult counterpart in a conserved BCR repertoire and rapid but transient response dynamics. These properties may account for the sensitivity of neonates to infections and limited effectivity of vaccination strategies. Finally, our findings have implications for a limited comparability of mouse models to human infant B cell immunity.