Structural diversity of B-cell receptor repertoires along the B-cell differentiation axis in humans and mice.

Autor: Aleksandr Kovaltsuk, Matthew I J Raybould, Wing Ki Wong, Claire Marks, Sebastian Kelm, James Snowden, Johannes Trück, Charlotte M Deane
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS Computational Biology, Vol 16, Iss 2, p e1007636 (2020)
Druh dokumentu: article
ISSN: 1553-734X
1553-7358
DOI: 10.1371/journal.pcbi.1007636
Popis: 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 complementary-determining regions (CDRs) of more than 180 million human and mouse B-cell receptor (BCR) repertoire sequences. These structurally annotated CDRs 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 CDR 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 CDR structure usage. Our results establish the CDR 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. The software tool for structural annotation of BCR repertoires, SAAB+, is available at https://github.com/oxpig/saab_plus.
Databáze: Directory of Open Access Journals
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