B cells play a central role in adaptive immune processes, mainly through the production of antibodies. Children are born without having had much contact with foreign antigens but through continuous exposure, the human immune system builds a repository of cells bearing diverse antigen-specific adaptive immune receptors that enable an effective secondary immune response. The maturation of the B-cell system through continuous antigen exposure with age is poorly studied.
We investigated the naïve and antigen-experienced B-cell receptor (BCR) repertoire in 46 healthy individuals aged 6m to 50y. Heavy chain BCR transcripts were amplified and sequenced with data analysis assessing repertoire characteristics and the self-reactive and structural nature of BCR transcripts.
The final dataset consisted of ~7M unique sequences. Most dynamics were observed in the first 10y of life characterized by alterations in immunoglobulin gene usage, 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 indicating that somatic hypermutation has driven specificity of these sequences away from self. Structural analysis revealed that the frequency of antibodies different from germline in shape increased with age.
This study demonstrates an extensive maturation of the B-cell system in the first 10 years of life in line with accumulating environmental antigen exposure. Further antibody repertoire alterations continue to be made thereafter, although at a lower rate. This study also provides a reference data set of BCR repertoires and stresses the importance of using well-selected, age-appropriate controls in future studies.