Maturation of naïve and antigen-experienced B-cell receptor repertoires with age

B cells play a central role in adaptive immune processes, mainly through the production of antibodies. The maturation of the B-cell system through continuous antigen exposure with age is poorly studied. We extensively investigated naive and antigen-experienced B-cell receptor (BCR) repertoires in individuals aged 6 months to 50 years. Most dynamics were observed in the first 10 years of life characterized by an increase in frequencies of mutated transcripts through positive selection, increased usage of downstream constant region genes and a decrease in the frequency of transcripts with self-reactive properties. Structural analysis revealed that the frequency of antibodies different from germline in shape increased with age. Our results suggest large and broad changes of BCR repertoires through childhood and stress the importance of using well-selected, age-appropriate controls in BCR studies.