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Structural Diversity of B-Cell Receptor Repertoires along the B-cell Differentiation Axis in Humans and Mice


Kovaltsuk, Aleksandr; Raybould, Matthew I J; Wong, Wing Ki; Marks, Claire; Kelm, Sebastian; Snowden, James; Trück, Johannes; Deane, Charlotte M (2019). Structural Diversity of B-Cell Receptor Repertoires along the B-cell Differentiation Axis in Humans and Mice. bioRxiv n/a, University of Zurich.

Abstract

Most current analysis tools for antibody next-generation sequencing data work with primary sequence descriptors, leaving accompanying structural information unharnessed. We have used novel rapid methods to structurally characterize the paratopes of more than 180 million human and mouse B-cell receptor (BCR) repertoire sequences. These structurally annotated paratopes provide unprecedented insights into both the structural predetermination and dynamics of the adaptive immune response. We show that B-cell types can be distinguished based solely on these structural properties. Antigen-unexperienced BCR repertoires use the highest number and diversity of paratope structures and these patterns of naïve repertoire paratope usage are highly conserved across subjects. In contrast, more differentiated B-cells are more personalized in terms of paratope structure usage. Our results establish the paratope structure differences in BCR repertoires and have applications for many fields including immunodiagnostics, phage display library generation, and “humanness” assessment of BCR repertoires from transgenic animals.

Abstract

Most current analysis tools for antibody next-generation sequencing data work with primary sequence descriptors, leaving accompanying structural information unharnessed. We have used novel rapid methods to structurally characterize the paratopes of more than 180 million human and mouse B-cell receptor (BCR) repertoire sequences. These structurally annotated paratopes provide unprecedented insights into both the structural predetermination and dynamics of the adaptive immune response. We show that B-cell types can be distinguished based solely on these structural properties. Antigen-unexperienced BCR repertoires use the highest number and diversity of paratope structures and these patterns of naïve repertoire paratope usage are highly conserved across subjects. In contrast, more differentiated B-cells are more personalized in terms of paratope structure usage. Our results establish the paratope structure differences in BCR repertoires and have applications for many fields including immunodiagnostics, phage display library generation, and “humanness” assessment of BCR repertoires from transgenic animals.

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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 15:24
Last Modified:23 Feb 2021 13:54
Series Name:bioRxiv
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/762880

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