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


Ghraichy, Marie; Galson, Jacob D; Kovaltsuk, Aleksandr; von Niederhäusern, Valentin; Pachlopnik Schmid, Jana; Miho, Enkelejda; Kelly, Dominic F; Deane, Charlotte M; Trück, Johannes (2019). Maturation of naïve and antigen-experienced B-cell receptor repertoires with age. bioRxiv n/a, University of Zurich.

Abstract

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 naïve 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.

Abstract

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 naïve 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.

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Additional indexing

Item Type:Working Paper
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2019
Deposited On:11 Dec 2019 15:17
Last Modified:19 Dec 2019 13:52
Series Name:bioRxiv
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/609651
Project Information:
  • : FunderSNSF
  • : Grant IDPZ00P3_161147
  • : Project TitleFunctional characterisation of the B cell compartment in children with antibody deficiency and following bone marrow transplantation
  • : FunderSNSF
  • : Grant IDPZ00P3_183777
  • : Project TitleCharacterization of human thymic B cells
  • : FunderGottfried und Julia Bangerter-Rhyner-Stiftung
  • : Grant ID
  • : Project Title
  • : FunderOlga Mayenfisch Stiftung
  • : Grant ID
  • : Project Title
  • : FunderPalatin-Stiftung
  • : Grant ID
  • : Project Title

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