Newborns begin producing their own antibodies within weeks of birth, rather than relying solely on maternal immunity for months, according to a study that disentangles infant- and mother-derived antibody repertoires with clonal precision.
The study applied intact LC-MS-based Fab profiling to compare IgA1 and IgG1 antibody repertoires across matched maternal serum, breast milk, and infant serum samples. By resolving antibodies at the clonal level, the approach allowed the team to track which antibodies persisted from the mother and which emerged de novo in the infant.
The researchers analyzed samples from four mother–infant pairs collected at birth and again 7–11 weeks postpartum. At birth, infant serum was dominated by maternal IgG1 – transferred across the placenta – while IgA1 was nearly absent. By the second timepoint, however, the antibody landscape had changed markedly. Clonal profiling showed that infant serum contained IgA1 and IgG1 antibodies that did not overlap with maternal serum or breast milk, indicating de novo antibody production by the infant.
For IgA1, clonal repertoire analysis showed that infant serum contained entirely new antibody clones that did not overlap with maternal serum or breast milk. This indicates that IgA1 detected in infant circulation at this stage is produced by the infant, rather than absorbed from milk. Similar patterns emerged for IgG1: although maternal IgG1 dominated infant serum at birth, a substantial fraction of new, infant-specific IgG1 clones appeared within the first two to three months of life.
Notably, the analysis found no convincing evidence that IgA antibodies from breast milk enter the infant bloodstream, challenging a common assumption about maternal antibody transfer. Instead, the data support a model in which milk IgA primarily acts at mucosal surfaces, while systemic humoral immunity is established rapidly by the infant.
The results suggest that infant antibody production begins earlier than commonly assumed, with implications for neonatal immune development and vaccination strategies. The authors note that MS-based clonal profiling provides a direct way to track these dynamics across maternal and infant compartments.
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